RBCC

Full text data of LIFR

LIFR [Confidence: high (a blood group or CD marker)]
Leukemia inhibitory factor receptor; LIF receptor; LIF-R (CD118; Flags: Precursor)

UniProt P42702
ID LIFR_HUMAN Reviewed; 1097 AA.
AC P42702; Q6LCD9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1995, sequence version 1.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Leukemia inhibitory factor receptor;
DE Short=LIF receptor;
DE Short=LIF-R;
DE AltName: CD_antigen=CD118;
DE Flags: Precursor;
GN Name=LIFR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=1915266;
RA Gearing D.P., Thut C.J., Vanden Bos T., Gimpel S.D., Delaney P.B.,
RA King J., Price V., Cosman D., Beckmann M.P.;
RT "Leukemia inhibitory factor receptor is structurally related to the
RT IL-6 signal transducer, gp130.";
RL EMBO J. 10:2839-2848(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 942-1097.
RA Wang Z., Melmed S.;
RT "Human LIF receptor 3' non-coding region.";
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP CHROMOSOMAL TRANSLOCATION WITH PLAG1.
RX PubMed=9525740; DOI=10.1038/sj.onc.1201660;
RA Voz M.L., Astrom A.-K., Kas K., Mark J., Stenman G.,
RA Van de Ven W.J.M.;
RT "The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas
RT results in upregulation of PLAG1 gene expression under control of the
RT LIFR promoter.";
RL Oncogene 16:1409-1416(1998).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-927, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 52-534, IDENTIFICATION IN A
RP COMPLEX WITH IL6ST; CNTF AND CNTFR, GLYCOSYLATION AT ASN-131; ASN-303;
RP ASN-407 AND ASN-426, DISULFIDE BONDS, ELECTRON MICROSCOPY, AND
RP SUBUNIT.
RX PubMed=18775332; DOI=10.1016/j.molcel.2008.08.011;
RA Skiniotis G., Lupardus P.J., Martick M., Walz T., Garcia K.C.;
RT "Structural organization of a full-length gp130/LIF-R cytokine
RT receptor transmembrane complex.";
RL Mol. Cell 31:737-748(2008).
RN [6]
RP VARIANT STWS PRO-279.
RX PubMed=14740318; DOI=10.1086/381715;
RA Dagoneau N., Scheffer D., Huber C., Al-Gazali L.I., Di Rocco M.,
RA Godard A., Martinovic J., Raas-Rothschild A., Sigaudy S., Unger S.,
RA Nicole S., Fontaine B., Taupin J.-L., Moreau J.-F., Superti-Furga A.,
RA Le Merrer M., Bonaventure J., Munnich A., Legeai-Mallet L.,
RA Cormier-Daire V.;
RT "Null leukemia inhibitory factor receptor (LIFR) mutations in Stueve-
RT Wiedemann/Schwartz-Jampel type 2 syndrome.";
RL Am. J. Hum. Genet. 74:298-305(2004).
RN [7]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-1068.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Signal-transducing molecule. May have a common pathway
CC with IL6ST. The soluble form inhibits the biological activity of
CC LIF by blocking its binding to receptors on target cells.
CC -!- SUBUNIT: Heterodimer composed of LIFR and IL6ST. The heterodimer
CC formed by LIFR and IL6ST interacts with the complex formed by CNTF
CC and CNTFR.
CC -!- SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: Isoform 2: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Membrane;
CC IsoId=P42702-1; Sequence=Displayed;
CC Name=2; Synonyms=Secreted;
CC IsoId=P42702-2; Sequence=Not described;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC folding and thereby efficient intracellular transport and cell-
CC surface receptor binding.
CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC activation.
CC -!- DISEASE: Stueve-Wiedemann syndrome (STWS) [MIM:601559]: Severe
CC autosomal recessive condition and belongs to the group of the
CC bent-bone dysplasias. SWS is characterized by bowing of the lower
CC limbs, with internal cortical thickening, wide metaphyses with
CC abnormal trabecular pattern, and camptodactyly. Additional
CC features include feeding and swallowing difficulties, as well as
CC respiratory distress and hyperthermic episodes, which cause death
CC in the first months of life. The rare survivors develop
CC progressive scoliosis, spontaneous fractures, bowing of the lower
CC limbs, with prominent joints and dysautonomia symptoms, including
CC temperature instability, absent corneal and patellar reflexes, and
CC smooth tongue. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- DISEASE: Note=A chromosomal aberration involving LIFR is found in
CC salivary gland pleiomorphic adenomas, the most common benign
CC epithelial tumors of the salivary gland. Translocation
CC t(5;8)(p13;q12) with PLAG1.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 2
CC subfamily.
CC -!- SIMILARITY: Contains 6 fibronectin type-III domains.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LIFR";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/LIFRID410ch5p13.html";
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DR EMBL; X61615; CAA43805.1; -; mRNA.
DR EMBL; U66563; AAB61897.1; -; mRNA.
DR PIR; S17308; S17308.
DR RefSeq; NP_001121143.1; NM_001127671.1.
DR RefSeq; NP_002301.1; NM_002310.5.
DR RefSeq; XP_005248359.1; XM_005248302.1.
DR RefSeq; XP_005248360.1; XM_005248303.1.
DR UniGene; Hs.133421; -.
DR PDB; 3E0G; X-ray; 3.10 A; A=52-534.
DR PDBsum; 3E0G; -.
DR ProteinModelPortal; P42702; -.
DR SMR; P42702; 52-822.
DR DIP; DIP-5770N; -.
DR MINT; MINT-1352123; -.
DR STRING; 9606.ENSP00000263409; -.
DR PhosphoSite; P42702; -.
DR DMDM; 1170784; -.
DR PaxDb; P42702; -.
DR PRIDE; P42702; -.
DR DNASU; 3977; -.
DR Ensembl; ENST00000263409; ENSP00000263409; ENSG00000113594.
DR Ensembl; ENST00000453190; ENSP00000398368; ENSG00000113594.
DR GeneID; 3977; -.
DR KEGG; hsa:3977; -.
DR UCSC; uc003jli.2; human.
DR CTD; 3977; -.
DR GeneCards; GC05M038475; -.
DR HGNC; HGNC:6597; LIFR.
DR HPA; CAB010252; -.
DR MIM; 151443; gene.
DR MIM; 601559; phenotype.
DR neXtProt; NX_P42702; -.
DR Orphanet; 3206; Stuve-Wiedemann syndrome.
DR PharmGKB; PA30371; -.
DR eggNOG; NOG147644; -.
DR HOGENOM; HOG000113324; -.
DR HOVERGEN; HBG006266; -.
DR InParanoid; P42702; -.
DR KO; K05058; -.
DR OMA; FYPDIPN; -.
DR OrthoDB; EOG7V49XP; -.
DR PhylomeDB; P42702; -.
DR SignaLink; P42702; -.
DR EvolutionaryTrace; P42702; -.
DR GeneWiki; Leukemia_inhibitory_factor_receptor; -.
DR GenomeRNAi; 3977; -.
DR NextBio; 15588; -.
DR PRO; PR:P42702; -.
DR ArrayExpress; P42702; -.
DR Bgee; P42702; -.
DR CleanEx; HS_LIFR; -.
DR Genevestigator; P42702; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0004923; F:leukemia inhibitory factor receptor activity; IDA:MGI.
DR GO; GO:0038165; P:oncostatin-M-mediated signaling pathway; IDA:GOC.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IDA:BHF-UCL.
DR Gene3D; 2.60.40.10; -; 5.
DR InterPro; IPR003961; Fibronectin_type3.
DR InterPro; IPR003529; Hematopoietin_rcpt_Gp130_CS.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF00041; fn3; 1.
DR SMART; SM00060; FN3; 5.
DR SUPFAM; SSF49265; SSF49265; 4.
DR PROSITE; PS50853; FN3; 5.
DR PROSITE; PS01353; HEMATOPO_REC_L_F2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane;
KW Chromosomal rearrangement; Complete proteome; Disease mutation;
KW Disulfide bond; Glycoprotein; Membrane; Phosphoprotein; Polymorphism;
KW Receptor; Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 44 Potential.
FT CHAIN 45 1097 Leukemia inhibitory factor receptor.
FT /FTId=PRO_0000010902.
FT TOPO_DOM 45 833 Extracellular (Potential).
FT TRANSMEM 834 858 Helical; (Potential).
FT TOPO_DOM 859 1097 Cytoplasmic (Potential).
FT DOMAIN 49 138 Fibronectin type-III 1.
FT DOMAIN 335 434 Fibronectin type-III 2.
FT DOMAIN 435 534 Fibronectin type-III 3.
FT DOMAIN 538 629 Fibronectin type-III 4.
FT DOMAIN 627 719 Fibronectin type-III 5.
FT DOMAIN 724 833 Fibronectin type-III 6.
FT MOTIF 519 523 WSXWS motif.
FT MOTIF 869 877 Box 1 motif.
FT MOD_RES 927 927 Phosphoserine.
FT CARBOHYD 64 64 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 85 85 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 131 131 N-linked (GlcNAc...).
FT CARBOHYD 143 143 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 191 191 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 243 243 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 303 303 N-linked (GlcNAc...).
FT CARBOHYD 390 390 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 407 407 N-linked (GlcNAc...).
FT CARBOHYD 426 426 N-linked (GlcNAc...).
FT CARBOHYD 445 445 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 481 481 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 489 489 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 572 572 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 652 652 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 663 663 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 680 680 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 729 729 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 787 787 N-linked (GlcNAc...) (Potential).
FT DISULFID 55 65
FT DISULFID 82 90
FT DISULFID 213 270
FT DISULFID 341 351
FT DISULFID 466 511
FT VARIANT 116 116 H -> Y (in dbSNP:rs3729734).
FT /FTId=VAR_029109.
FT VARIANT 279 279 S -> P (in STWS).
FT /FTId=VAR_025666.
FT VARIANT 578 578 D -> N (in dbSNP:rs3729740).
FT /FTId=VAR_029110.
FT VARIANT 633 633 I -> M (in dbSNP:rs2303743).
FT /FTId=VAR_021996.
FT VARIANT 664 664 S -> L (in dbSNP:rs3729744).
FT /FTId=VAR_038626.
FT VARIANT 785 785 V -> I (in dbSNP:rs3110234).
FT /FTId=VAR_029111.
FT VARIANT 1068 1068 F -> L (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036166.
FT STRAND 55 59
FT STRAND 62 66
FT STRAND 71 73
FT STRAND 79 83
FT STRAND 85 87
FT STRAND 89 97
FT STRAND 104 106
FT STRAND 110 113
FT STRAND 145 147
FT TURN 148 151
FT STRAND 152 159
FT HELIX 161 163
FT STRAND 169 181
FT STRAND 183 192
FT HELIX 194 196
FT STRAND 199 206
FT STRAND 216 225
FT STRAND 231 233
FT STRAND 242 244
FT STRAND 254 256
FT STRAND 258 262
FT STRAND 267 271
FT STRAND 277 284
FT STRAND 293 295
FT STRAND 297 301
FT STRAND 312 320
FT STRAND 322 330
FT STRAND 337 345
FT STRAND 348 354
FT HELIX 363 365
FT STRAND 368 373
FT TURN 374 376
FT STRAND 379 382
FT STRAND 393 398
FT STRAND 406 413
FT STRAND 418 425
FT HELIX 427 430
FT STRAND 437 441
FT STRAND 444 448
FT STRAND 451 454
FT STRAND 467 471
FT STRAND 473 475
FT STRAND 479 481
FT STRAND 488 491
FT STRAND 501 504
FT STRAND 506 510
SQ SEQUENCE 1097 AA; 123743 MW; C8602897E359FCE5 CRC64;
MMDIYVCLKR PSWMVDNKRM RTASNFQWLL STFILLYLMN QVNSQKKGAP HDLKCVTNNL
QVWNCSWKAP SGTGRGTDYE VCIENRSRSC YQLEKTSIKI PALSHGDYEI TINSLHDFGS
STSKFTLNEQ NVSLIPDTPE ILNLSADFST STLYLKWNDR GSVFPHRSNV IWEIKVLRKE
SMELVKLVTH NTTLNGKDTL HHWSWASDMP LECAIHFVEI RCYIDNLHFS GLEEWSDWSP
VKNISWIPDS QTKVFPQDKV ILVGSDITFC CVSQEKVLSA LIGHTNCPLI HLDGENVAIK
IRNISVSASS GTNVVFTTED NIFGTVIFAG YPPDTPQQLN CETHDLKEII CSWNPGRVTA
LVGPRATSYT LVESFSGKYV RLKRAEAPTN ESYQLLFQML PNQEIYNFTL NAHNPLGRSQ
STILVNITEK VYPHTPTSFK VKDINSTAVK LSWHLPGNFA KINFLCEIEI KKSNSVQEQR
NVTIKGVENS SYLVALDKLN PYTLYTFRIR CSTETFWKWS KWSNKKQHLT TEASPSKGPD
TWREWSSDGK NLIIYWKPLP INEANGKILS YNVSCSSDEE TQSLSEIPDP QHKAEIRLDK
NDYIISVVAK NSVGSSPPSK IASMEIPNDD LKIEQVVGMG KGILLTWHYD PNMTCDYVIK
WCNSSRSEPC LMDWRKVPSN STETVIESDE FRPGIRYNFF LYGCRNQGYQ LLRSMIGYIE
ELAPIVAPNF TVEDTSADSI LVKWEDIPVE ELRGFLRGYL FYFGKGERDT SKMRVLESGR
SDIKVKNITD ISQKTLRIAD LQGKTSYHLV LRAYTDGGVG PEKSMYVVTK ENSVGLIIAI
LIPVAVAVIV GVVTSILCYR KREWIKETFY PDIPNPENCK ALQFQKSVCE GSSALKTLEM
NPCTPNNVEV LETRSAFPKI EDTEIISPVA ERPEDRSDAE PENHVVVSYC PPIIEEEIPN
PAADEAGGTA QVIYIDVQSM YQPQAKPEEE QENDPVGGAG YKPQMHLPIN STVEDIAAEE
DLDKTAGYRP QANVNTWNLV SPDSPRSIDS NSEIVSFGSP CSINSRQFLI PPKDEDSPKS
NGGGWSFTNF FQNKPND
//

MIM 151443
*RECORD*
*FIELD* NO
151443
*FIELD* TI
*151443 LEUKEMIA INHIBITORY FACTOR RECEPTOR; LIFR
*FIELD* TX

CLONING

Gearing et al. (1991) isolated a cDNA clone encoding the human LIF
read morereceptor by expression screening of a human placenta cDNA library. The
LIFR gene encodes a 1,097-amino acid transmembrane protein that is
composed of 6 different domains: 2 cytokine receptor homology domains
(CRH1 and CRH2), 1 immunoglobulin-like domain, 1 type III fibronectin
domain with 3 modules, 1 transmembrane domain, and 1 cytoplasmic domain.

GENE STRUCTURE

The LIFR gene contains 20 exons (Tomida and Gotoh, 1996).

GENE FUNCTION

The LIF receptor (LIFR) is the low-affinity binding chain that, together
with the high-affinity converter subunit gp130 (600694), forms a
high-affinity receptor complex that mediates the action of the
leukemia-inhibitory factor (LIF; 159540). LIF is a polyfunctional
cytokine that affects the differentiation, survival, and proliferation
of a wide variety of cells in the adult and the embryo (Gearing et al.,
1993). The high-affinity complex also binds a related cytokine,
oncostatin M (OSM; 165095). Both LIFR and gp130 are members of a family
of cytokine receptors that includes components of the receptors for the
majority of hematopoietic cytokines and for cytokines that affect other
systems, including the ciliary neurotrophic factor (CNTF; 118945),
growth hormone (GH; 139250), and prolactin (PRL; 176760).

Bozec et al. (2008) demonstrated that the FOS-related protein FRA2
(601575) controls osteoclast survival and size. They observed that bones
of Fra2-deficient newborn mice had giant osteoclasts, and signaling
through LIF and its receptor LIFR was impaired. Similarly, newborn
animals lacking Lif had giant osteoclasts, and Bozec et al. (2008)
demonstrated that LIF is a direct transcriptional target of FRA2 and
c-JUN (604641). Moreover, bones deficient in Fra2 and Lif were hypoxic
and expressed increased levels of hypoxia-induced factor 1-alpha (HIF1A;
603348) and Bcl2 (151430). Overexpression of Bcl2 was sufficient to
induce giant osteoclasts in vivo, whereas Fra2 and Lif affected Hif1a
through transcriptional modulation of the Hif prolyl hydroxylase Phd2
(606425). This pathway is operative in the placenta, because specific
inactivation of Fra2 in the embryo alone did not cause hypoxia or the
giant osteoclast phenotype. Bozec et al. (2008) concluded that thus,
placenta-induced hypoxia during embryogenesis leads to the formation of
giant osteoclasts in young pups.

MAPPING

Using somatic cell hybrid analysis, Gearing et al. (1993) demonstrated
that the human LIFR gene is located on 5p13-p12. By interspecific
backcross analysis, they showed that the murine locus is on chromosome
15 in a region of homology with human chromosome 5p. In both human and
mouse genomes, the LIFR locus was linked to the genes encoding the
receptors for interleukin-7 (IL7R; 146661), prolactin (PRLR; 176761),
and growth hormone (GHR; 600946).

MOLECULAR GENETICS

Stuve-Wiedemann syndrome (STWS; 601559) is a severe autosomal recessive
disorder characterized by bowing of the long bones, with cortical
thickening, flared metaphyses with coarsened trabecular pattern,
camptodactyly, respiratory distress, feeding difficulties, and
hyperthermic episodes responsible for early lethality. Clinical overlap
with Schwartz-Jampel type 2 syndrome (SJS2) suggested that STWS and SJS2
could be allelic disorders; see 601559. Through studying a series of 19
families with STWS/SJS2, Dagoneau et al. (2004) mapped the disease gene
to 5p13.1 at locus D5S418 and identified 14 distinct null mutations in
the 19 families. An identical frameshift insertion (653_654insT;
151443.0001) was identified in families from the United Arab Emirates,
suggesting founder effect. Twelve of the 14 mutations predicted
premature termination of translation. Functional studies indicated that
these mutations altered the stability of LIFR mRNA transcripts,
resulting in the absence of the LIFR protein and the impairment of the
JAK/STAT3 signaling pathway in patient cells. The authors concluded that
STWS and SJS2 are indeed a single clinically and genetically homogeneous
condition due to null mutations in the LIFR gene. Dagoneau et al. (2004)
had considered LIFR to be a good candidate gene because, in addition to
its map location, Lifr -/- mice present with reduction of fetal bone
volume, with an increased volume of osteoclasts, reduction of astrocyte
numbers in spinal cord and brain, and perinatal death (Ware et al.,
1995).

*FIELD* AV
.0001
STUVE-WIEDEMANN/SCHWARTZ-JAMPEL TYPE 2 SYNDROME
LIFR, 1-BP INS, 653T

In 5 Omani and Yemeni families originating from the United Arab
Emirates, all with consanguineous parents, Dagoneau et al. (2004) found
that children with Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome
(601559) had a 1-bp insertion, 653_654insT, in exon 6 of the LIFR gene
causing frameshift and a stop 2 codons downstream.

.0002
STUVE-WIEDEMANN/SCHWARTZ-JAMPEL TYPE 2 SYNDROME
LIFR, ARG597TER

In a family from Portugal, in 2 Gypsy families, and in 1 French family,
Dagoneau et al. (2004) found that the STWS/SJS2 syndrome (601559) was
associated with homozygosity for an arg597-to-stop (R597X) mutation in
exon 13 of the LIFR gene. This same mutation was found in compound
heterozygous state in 2 affected members of a Swiss family, the other
mutation being a 1-bp insertion, 2011_2012insT (151443.0003), which
resulted in frameshift and a stop 12 codons downstream.

.0003
STUVE-WIEDEMANN/SCHWARTZ-JAMPEL TYPE 2 SYNDROME
LIFR, 1-BP INS, 2011T

See 151443.0002 and Dagoneau et al. (2004).

.0004
STUVE-WIEDEMANN/SCHWARTZ-JAMPEL TYPE 2 SYNDROME
LIFR, 4-BP DEL, 167TAAC

In a girl with Stuve-Wiedemann syndrome (601559), born of consanguineous
Portuguese Gypsy parents, Gaspar et al. (2008) identified a homozygous
4-bp deletion (167delTAAC) in exon 3 of the LIFR gene, resulting in a
frameshift and premature termination. The child was alive at age 12
years and showed typical signs of the disorder, including bowed limbs,
facial dysmorphism, and later-onset dysautonomia. Gaspar et al. (2008)
noted that survival past infancy is unusual in this disorder.

*FIELD* RF
1. Bozec, A.; Bakiri, L.; Hoebertz, A.; Eferl, R.; Schilling, A. F.;
Komnenovic, V.; Scheuch, H.; Priemel, M.; Stewart, C. L.; Amling,
M.; Wagner, E. F.: Osteoclast size is controlled by Fra-2 through
LIF/LIF-receptor signalling and hypoxia. Nature 454: 221-225, 2008.

2. Dagoneau, N.; Scheffer, D.; Huber, C.; Al-Gazali, L. I.; Di Rocco,
M.; Godard, A.; Martinovic, J.; Raas-Rothschild, A.; Sigaudy, S.;
Unger, S.; Nicole, S.; Fontaine, B.; Taupin, J.-L.; Moreau, J.-F.;
Superti-Furga, A.; Le Merrer, M.; Bonaventure, J.; Munnich, A.; Legeai-Mallet,
L.; Cormier-Daire, V.: Null leukemia inhibitory factor receptor (LIFR)
mutations in Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome. Am.
J. Hum. Genet. 74: 298-305, 2004.

3. Gaspar, I. M.; Saldanha, T.; Cabral, P.; Vilhena, M. M.; Tuna,
M.; Costa, C.; Dagoneau, N.; Daire, V. C.; Hennekam, R. C. M.: Long-term
follow-up in Stuve-Wiedemann syndrome: a clinical report. Am. J.
Med. Genet. 146A: 1748-1753, 2008.

4. Gearing, D. P.; Druck, T.; Huebner, K.; Overhauser, J.; Gilbert,
D. J.; Copeland, N. G.; Jenkins, N. A.: The leukemia inhibitory factor
receptor (LIFR) gene is located within a cluster of cytokine receptor
loci on mouse chromosome 15 and human chromosome 5p12-p13. Genomics 18:
148-150, 1993.

5. Gearing, D. P.; Thut, C. J.; VandenBos, T.; Gimpel, S. D.; Delaney,
P. B.; King, J.; Price, V.; Cosman, D.; Beckmann, M. P.: Leukemia
inhibitory factor receptor is structurally related to the IL-6 signal
transducer, gp130. EMBO J. 10: 2839-2848, 1991.

6. Tomida, M.; Gotoh, O.: Structure of the gene encoding the human
differentiation-stimulating factor/leukemia inhibitory factor receptor. J.
Biochem. 120: 201-205, 1996.

7. Ware, C. B.; Horowitz, M. C.; Renshaw, B. R.; Hunt, J. S.; Liggitt,
D.; Koblar, S. A.; Gliniak, B. C.; McKenna, H. J.; Papayannopoulou,
T.; Thoma, B.; Cheng, L.; Donovan, P. J.; Peschon, J. J.; Bartlett,
P. F.; Willis, C. R.; Wright, B. D.; Carpenter, M. K.; Davison, B.
L.; Gearing, D. P.: Targeted disruption of the low-affinity leukemia
inhibitory factor receptor gene causes placental, skeletal, neural
and metabolic defects and results in perinatal death. Development 121:
1283-1299, 1995.

*FIELD* CN
Cassandra L. Kniffin - updated: 9/9/2008
Ada Hamosh - updated: 8/8/2008
Victor A. McKusick - updated: 2/5/2004

*FIELD* CD
Victor A. McKusick: 10/14/1993

*FIELD* ED
carol: 09/16/2013
wwang: 9/11/2008
ckniffin: 9/9/2008
alopez: 8/27/2008
terry: 8/8/2008
carol: 10/18/2005
terry: 2/10/2005
terry: 6/18/2004
alopez: 3/30/2004
alopez: 2/9/2004
terry: 2/5/2004
jlewis: 7/27/1999
carol: 10/19/1993
carol: 10/14/1993

MIM 601559
*RECORD*
*FIELD* NO
601559
*FIELD* TI
#601559 STUVE-WIEDEMANN SYNDROME
;;STWS; SWS;;
SCHWARTZ-JAMPEL SYNDROME, TYPE 2; SJS2;;
read moreSCHWARTZ-JAMPEL SYNDROME, NEONATAL;;
STUVE-WIEDEMANN/SCHWARTZ-JAMPEL TYPE 2 SYNDROME
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
Stuve-Wiedemann syndrome (STWS), also known as neonatal Schwartz-Jampel
syndrome type 2 (SJS2), is caused by mutation in the leukemia inhibitory
factor receptor gene (LIFR; 151443) on chromosome 5p13.

DESCRIPTION

Stuve-Wiedemann syndrome (STWS) is an autosomal recessive disorder
characterized by bowing of the long bones and other skeletal anomalies,
episodic hyperthermia, and respiratory and feeding distress usually
resulting in early death (Dagoneau et al., 2004).

See also 'classic' Schwartz-Jampel syndrome type 1 (SJS1; 255800), a
phenotypically similar but genetically distinct disorder caused by
mutation in the HSPG2 gene (142461) on chromosome 1p36.1-p34.

CLINICAL FEATURES

Stuve and Wiedemann (1971) reported 2 sisters and a first-cousin male
with congenital bowing of the long bones. Other features included short
stature, camptodactyly with ulnar deviation, and contractures of the
elbows and fingers. Radiographically, the long bones were short and
thick with large metaphyses. Although the clavicles were normal, there
was a broad coracoid process bilaterally, long scapulae, and relatively
thin ribs. The pubic and ischial bones were broad and the ilia
relatively small. One patient died after 10 days of life from
respiratory insufficiency with apnea; her sister developed hyperthermia
with temperatures as high as 41 degrees centigrade and died on day 5 of
life. The male first cousin to these 2 girls had identical congenital
flexion contractures of the fingers and toes and died of respiratory
insufficiency as a neonate. The parents of the 2 sibships were related;
the mothers were sisters and the fathers were brothers. Stuve and
Wiedemann (1971) postulated that the disorder in this family represented
a specific condition.

Farrell et al. (1987) described a newborn male with severe
manifestations resulting in death at 12 days of age.

Kozlowski and Tenconi (1996) reported a 3-year-old boy with
Stuve-Wiedemann syndrome. At age 30 months, he had short limbs with an
increased upper to lower segment ratio, bowing of the femora, tibiae,
and radii, with decreased extension at the knees and elbows. He had
short fingers with flexion of all the small joints in the hand and
adduction of the thumb, as well as camptodactyly of the second through
fourth fingers. Talipes valgus was observed. On radiographic
examination, bowing of the long bones of the lower limbs and forearms
was documented; wide metaphyses with decreased density and abnormal
trabecular pattern were also seen. Kozlowski and Tenconi (1996)
discussed the differential diagnosis of Stuve-Wiedemann syndrome,
campomelic dysplasia (114290), and kyphomelic dysplasia (211350).

Al-Gazali (1993) and Al-Gazali et al. (1996) reported 11 children in 5
families from the United Arab Emirates with what they termed 'severe
neonatal Schwartz-Jampel syndrome type 2.' All presented at birth with
skeletal abnormalities and feeding difficulties. Five had the typical
pursed appearance of the mouth. Nine died from respiratory
complications: 5 in the neonatal period and 4 before 2 years of age. The
patients were mostly of Omani origin. Only 7 of 17 previously reported
neonatal SJS cases had a similar severe course, suggesting to Al-Gazali
et al. (1996) that there is a subgroup of SJS with severe respiratory
and feeding problems, poor prognosis, and early death.

Chabrol et al. (1997) reported 3 newborn boys from 2 consanguineous
Gypsy families with manifestations of Stuve-Wiedemann syndrome. The 2
families were presumably unrelated. Two of the infants died shortly
after birth, whereas the third was alive at the age of 1 year. Besides
hyperthermic episodes, 1 patient had hyperaminoaciduria, hepatic
failure, and megaloblastic anemia, which prompted investigation of the
mitochondrial respiratory chain in 2 cases. Abnormal results consisting
of decreased activities of complexes I and IV were found in both
patients. The finding of the Stuve-Wiedemann phenotype and abnormal
mitochondrial metabolism from each of 2 infants from different families
supported a pathogenetic relationship between the 2. Radiographs of the
bony angulations were displayed.

Giedion et al. (1997) reported 2 sibs with neonatal SJS. One of them
showed short, bowed femora and fetal hypokinesia on ultrasound at 17
weeks' gestation. Both were severely affected with mask-like facies,
myopia, and multiple skeletal anomalies. One died at age 3 months,
whereas the other was alive at age 9 years with normal intelligence, but
was severely physically handicapped. Linkage was excluded from the SJS1
locus on chromosome 1p.

Cormier-Daire et al. (1998) reported findings in 8 patients with STWS
suggesting that the syndrome is clinically homogeneous. All patients had
feeding and swallowing difficulties, respiratory insufficiency, abnormal
appearance, muscle hypotonia, and postnatal short stature. Recurrent
episodes of unexplained fever occurred in all and were the cause of
death in 6 of the 8 patients. Parental consanguinity and sib recurrence
suggested autosomal recessive inheritance.

Cormier-Daire et al. (1998) suggested that STWS and neonatal
Schwartz-Jampel syndrome, or SJS type 2, were the same entity based on
similar clinical, radiologic, and histologic features. Superti-Furga et
al. (1998) also concluded that Schwartz-Jampel syndrome type 2 and
Stuve-Wiedemann syndrome should be considered the same entity. To test
for possible nosologic identity between these disorders, they reviewed
the literature and obtained a follow-up of the only 2 surviving
patients, one with SJS type 2 at age 10 years and another with STWS at
age 7 years. Patients reported as having either neonatal SJS or STWS
presented a combination of a severe, prenatal-onset neuromuscular
disorder with congenital joint contractures, respiratory and feeding
difficulties, tendency to hyperthermia, and frequent death in infancy
and a distinct campomelic-metaphyseal skeletal dysplasia. The follow-up
observation of an identical and unique pattern of progressive bone
dysplasia in the 2 patients (one with SJS type 2, one with STWS)
surviving beyond infancy added to the evidence in favor of identity.

Raas-Rothschild et al. (2003) reported 2 sibs with Stuve-Wiedemann
syndrome who died of respiratory failure due to pulmonary hypertension.
The parents were first-cousin Muslim Arabs originating from the
Jerusalem area. Echocardiographic and postmortem analysis showed that
both patients had a closed ductus arteriosus, dilated pulmonary arteries
with extremely hypertrophied walls, and right-to-left shunting through a
patent foramen ovale. The authors postulated a mechanism in which
antenatal premature closure of the ductus arteriosus could result in
increased right ventricular afterload and increased pulmonary artery
pressure, ultimately causing pulmonary artery hypertrophy and
hypertension. Raas-Rothschild et al. (2003) suggested that some patients
with Stuve-Wiedemann syndrome and early neonatal death due to
respiratory failure may have had pulmonary hypertension.

- Patients with Longer Survival

Stuve-Wiedemann syndrome is typically lethal in the neonatal period.
Chen et al. (2001), who described the case of a child surviving to age 9
years, stated that only 2 patients with long survival had been reported.
In addition to characteristic features of STWS, their patient had a
number of unique clinical signs, including lack of corneal and patellar
reflexes, smooth tongue with no fungiform papillae, chronic gingival
abscesses, mottled and otherwise poor dentition, blotchy pigmentation of
the skin, unusual infections, multiple fractures, and progressive
scoliosis. Cytogenetic analysis identified mosaicism for a supernumerary
marker chromosome, seen in the majority of amniocytes, blood cells, and
skin fibroblasts. The marker chromosome was shown to be derived from
chromosome 5 and to contain euchromatin.

Al-Gazali et al. (2003) reported 3 children from 2 inbred Arab families
with Stuve-Wiedemann syndrome who had survived the first year of life;
their ages were 6, 2.8, and 2 years. All exhibited a characteristic
phenotype resembling that described by Chen et al. (2001). In all 3
children, the skeletal abnormalities progressed to severe bowing of the
long bones with prominent joints and severe spinal deformity. All
exhibited neurologic symptoms including temperature instability with
excessive sweating, reduced pain sensation with repeated injury to the
tongue and limbs, absent corneal reflexes, and a smooth tongue. All 3
children had normal intelligence. Radiologic changes included
undertubulation of the diaphyses, rarefaction and striation of
metaphyses, destruction of the femoral heads, and spinal deformity. This
report confirmed that survival in this syndrome is possible and that the
prognosis improves after the first year of life. It also supported the
existence of a characteristic phenotype in Stuve-Wiedemann syndrome
survivors that includes neurologic symptoms reminiscent of dysautonomia
in addition to the skeletal abnormalities and distinctive radiologic
features.

Gaspar et al. (2008) reported long-term follow-up of a 12-year-old girl,
born of consanguineous Portuguese Gypsy parents, with STWS confirmed by
genetic analysis (151443.0004). Early in infancy she had hypotonia,
facial myotonia, low-set ears, a short neck, short bowed limbs,
contractures of the elbows and knees, camptodactyly, and talipes
equinovarus. She was a poor feeder and had recurrent bouts of fever and
recurrent respiratory problems. In the ensuing years, she developed
severe corneal opacities, progressive scoliosis, more prominent joint
contractures, and ulnar deviation of the hands. Autonomic instability
included poor body temperature regulation, with asymmetric and
paradoxical sweating, and areas of hypoperfusion and hyperperfusion of
the trunk and extremities. Her cognitive development was excellent.
Other features included absent corneal reflexes, smooth tongue, and poor
dentition with chronic dental abscesses. She lost her ability to walk
and became wheelchair dependent at age 9. In a review of the few STWS
patients with long survival, Gaspar et al. (2008) concluded that the
major symptoms influencing daily life in these patients are loss of
vision, paradoxical sweating/shivering, severe spinal deformity,
spontaneous fractures, and limited mobility.

INHERITANCE

Wiedemann and Stuve (1996) gave an update and a historical footnote, and
noted that reported cases were consistent with autosomal recessive
inheritance.

MAPPING

Giedion et al. (1997) and Brown et al. (1997) demonstrated that neonatal
Schwartz-Jampel syndrome type 2 was not linked to chromosome 1p36.1-p34,
where 'classic' Schwartz-Jampel syndrome maps.

Through a study of a series of 19 patients with STWS/SJS2, Dagoneau et
al. (2004) mapped the disease gene to chromosome 5p13.1 at marker
D5S418.

MOLECULAR GENETICS

In patients with Stuve-Wiedemann syndrome, Dagoneau et al. (2004)
identified mutations in the leukemia inhibitory factor receptor gene
(LIFR; see, e.g., 151443.0001-151443.0003). Some of the patients had
been reported earlier by Al-Gazali et al. (1996, 2003), Chabrol et al.
(1997), Cormier-Daire et al. (1998), and Superti-Furga et al. (1998).

NOMENCLATURE

Chabrol et al. (1997) used the abbreviation SWS for this disorder, but
this abbreviation had already been used for Sturge-Weber syndrome
(185300).

*FIELD* RF
1. Al-Gazali, L. I.: The Schwartz-Jampel syndrome. Clin. Dysmorph. 2:
47-54, 1993.

2. Al-Gazali, L. I.; Ravenscroft, A.; Feng, A.; Shubbar, A.; Al-Saggaf,
A.; Haas, D.: Stuve-Wiedemann syndrome in children surviving infancy:
clinical and radiological features. Clin. Dysmorph. 12: 1-8, 2003.

3. Al-Gazali, L. I.; Varghese, M.; Varady, E.; Al Talabani, J.; Scorer,
J.; Bakalinova, D.: Neonatal Schwartz-Jampel syndrome: a common autosomal
recessive syndrome in the United Arab Emirates. J. Med. Genet. 33:
203-211, 1996.

4. Brown, K. A.; Al-Gazali, L. I.; Moynihan, L. M.; Lench, N. J.;
Markham, A. F.; Mueller, R. F.: Genetic heterogeneity in Schwartz-Jampel
syndrome: two families with neonatal Schwartz-Jampel syndrome do not
map to human chromosome 1p34-p36.1. J. Med. Genet. 34: 685-687,
1997.

5. Chabrol, B.; Sigaudy, S.; Paquis, V.; Montfort, M.-F.; Giudicelli,
H.; Pellissier, J.-F.; Millet, V.; Mancini, J.; Philip, N.: Stuve-Wiedemann
syndrome and defects of the mitochondrial respiratory chain. Am.
J. Med. Genet. 72: 222-226, 1997.

6. Chen, E.; Cotter, P. D.; Cohen, R. A.; Lachman, R. S.: Characterization
of a long-term survivor with Stuve-Wiedemann syndrome and mosaicism
of a supernumerary marker chromosome. Am. J. Med. Genet. 101: 240-245,
2001.

7. Cormier-Daire, V.; Superti-Furga, A.; Munnich, A.; Lyonnet, S.;
Rustin, P.; Delezoide, A. L.; De Lonlay, P.; Giedion, A.; Maroteaux,
P.; Le Merrer, M.: Clinical homogeneity of the Stuve-Wiedemann syndrome
and overlap with the Schwartz-Jampel syndrome type 2. Am. J. Med.
Genet. 78: 146-149, 1998.

8. Dagoneau, N.; Scheffer, D.; Huber, C.; Al-Gazali, L. I.; Di Rocco,
M.; Godard, A.; Martinovic, J.; Raas-Rothschild, A.; Sigaudy, S.;
Unger, S.; Nicole, S.; Fontaine, B.; Taupin, J.-L.; Moreau, J.-F.;
Superti-Furga, A.; Le Merrer, M.; Bonaventure, J.; Munnich, A.; Legeai-Mallet,
L.; Cormier-Daire, V.: Null leukemia inhibitory factor receptor (LIFR)
mutations in Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome. Am.
J. Hum. Genet. 74: 298-305, 2004.

9. Farrell, S. A.; Davidson, R. G.; Thorp, P.: Neonatal manifestations
of Schwartz-Jampel syndrome. Am. J. Med. Genet. 27: 799-805, 1987.

10. Gaspar, I. M.; Saldanha, T.; Cabral, P.; Vilhena, M. M.; Tuna,
M.; Costa, C.; Dagoneau, N.; Daire, V. C.; Hennekam, R. C. M.: Long-term
follow-up in Stuve-Wiedemann syndrome: a clinical report. Am. J.
Med. Genet. 146A: 1748-1753, 2008.

11. Giedion, A.; Boltshauser, E.; Briner, J.; Eich, G.; Exner, G.;
Fendel, H.; Kaufmann, L.; Steinmann, B.; Spranger, J.; Superti-Furga,
A.: Heterogeneity in Schwartz-Jampel chondrodystrophic myotonia. Europ.
J. Pediat. 156: 214-223, 1997.

12. Kozlowski, K.; Tenconi, R.: Stuve-Wiedemann dysplasia in a 3.5-year-old
boy. Am. J. Med. Genet. 63: 17-19, 1996.

13. Raas-Rothschild, A.; Ergaz-Schaltiel, Z.; Bar-Ziv, J.; Rein, A.
J. J. T.: Cardiovascular abnormalities associated with the Stuve-Wiedemann
syndrome. Am. J. Med. Genet. 121A: 156-158, 2003.

14. Stuve, A.; Wiedemann, H.-R.: Congenital bowing of the long bones
in two sisters. (Letter) Lancet 298: 495 only, 1971. Note: Originally
Volume 2.

15. Superti-Furga, A.; Tenconi, R.; Clementi, M.; Eich, G.; Steinmann,
B.; Boltshauser, E.; Giedion, A.: Schwartz-Jampel syndrome type 2
and Stuve-Wiedemann syndrome: a case for 'lumping.' Am. J. Med. Genet. 78:
150-154, 1998.

16. Wiedemann, H.-R.; Stuve, A.: Stuve-Wiedemann syndrome: update
and historical footnote. Am. J. Med. Genet. 63: 12-16, 1996.

*FIELD* CS
INHERITANCE:
Autosomal recessive

GROWTH:
[Height];
Short stature, postnatal

HEAD AND NECK:
[Face];
Frontal bossing;
Midface hypoplasia;
Square face;
Micrognathia;
Facial myotonia;
[Ears];
Low-set ears;
[Eyes];
Absent corneal reflexes (reported in older children);
Decreased blink reflexes;
Short palpebral fissures;
Corneal opacities;
[Nose];
Short nose;
Wide nasal base;
[Mouth];
Pursed lips;
Smooth tongue without fungiform papillae (in older children);
Ulcers of the tongue due to decreased sensation;
[Teeth];
Poor dentition (in older children);
Mottled enamel;
Chronic tooth abscesses;
[Neck];
Short neck

CARDIOVASCULAR:
[Vascular];
Pulmonary artery hypertension;
Hypertrophy of the pulmonary artery wall

RESPIRATORY:
Respiratory insufficiency;
Apnea;
[Lung];
Pulmonary hypoplasia

CHEST:
[Ribs, sternum, clavicles, and scapulae];
Broad coracoid processes;
Long scapulae;
Thin ribs

ABDOMEN:
[Gastrointestinal];
Poor feeding;
Swallowing difficulties (dysphagia)

SKELETAL:
Spontaneous fracture (in older children);
Osteoporosis;
[Spine];
Scoliosis, progressive;
[Pelvis];
Broad pubic bones;
Broad ischial bones;
Relatively small ilia;
[Limbs];
Camptomelia;
Congenital bowing of the long bones (lower extremity greater than
upper extremity);
Short, thick long bones;
Bowed, short femora;
Bowed, short tibiae;
Cortical thickening of the long bones;
Long bones have wide, flared metaphyses with decreased density;
Radiolucent metaphyses have abnormal trabecular pattern;
Rarefaction of the metaphyses;
Striation of the metaphyses;
Undertubulation of the diaphyses;
Camptodactyly with ulnar deviation;
Contractures of the knees;
Contractures of the elbows;
Prominent joints (in older children);
[Hands];
Flexion contractures of the fingers;
Camptodactyly;
Ulnar deviation of the fingers;
Short fingers;
Adducted thumbs;
[Feet];
Flexion contractures of the toes;
Talipes valgus

SKIN, NAILS, HAIR:
[Skin];
Blotching pigmentation of the skin (in older children);
Thin skin;
Single palmar crease

MUSCLE, SOFT TISSUE:
Hypotonia

NEUROLOGIC:
[Central nervous system];
Dysautonomia;
Normal intelligence;
[Peripheral nervous system];
Decreased pain sensation in extremities;
Absent patellar reflexes

VOICE:
Hoarse voice;
Hypernasal voice

METABOLIC FEATURES:
Hyperthermia, episodic;
Poor temperature regulation

MISCELLANEOUS:
Death in infancy due to hyperthermia or apnea;
Survival past infancy is rare;
Survivors develop dysautonomia-like symptoms

MOLECULAR BASIS:
Caused by mutations in the leukemia inhibitory factor receptor gene
(LIFR, 151443.0001)

*FIELD* CN
Kelly A. Przylepa - revised: 10/12/2005
Cassandra L. Kniffin - revised: 10/6/2005

*FIELD* CD
John F. Jackson: 9/23/1998

*FIELD* ED
joanna: 07/03/2013
joanna: 9/10/2008
ckniffin: 9/9/2008
joanna: 11/9/2005
joanna: 10/12/2005
ckniffin: 10/6/2005
alopez: 2/9/2004

*FIELD* CN
Cassandra L. Kniffin - updated: 9/9/2008
Cassandra L. Kniffin - updated: 10/5/2005
Siobhan M. Dolan - updated: 4/28/2004
Victor A. McKusick - updated: 2/5/2004
Victor A. McKusick - updated: 7/31/2001
Victor A. McKusick - updated: 10/16/1998
Victor A. McKusick - updated: 9/2/1998
Victor A. McKusick - updated: 10/20/1997

*FIELD* CD
Clair A. Francomano: 12/6/1996

*FIELD* ED
terry: 04/13/2009
wwang: 9/11/2008
ckniffin: 9/9/2008
ckniffin: 1/2/2007
wwang: 10/18/2005
wwang: 10/12/2005
ckniffin: 10/5/2005
carol: 4/29/2004
terry: 4/28/2004
alopez: 2/9/2004
terry: 2/5/2004
cwells: 8/10/2001
cwells: 8/2/2001
terry: 7/31/2001
carol: 9/13/1999
jlewis: 9/3/1999
carol: 12/2/1998
carol: 10/21/1998
terry: 10/16/1998
alopez: 9/8/1998
terry: 9/2/1998
carol: 5/27/1998
jenny: 10/21/1997
terry: 10/20/1997
terry: 7/8/1997
alopez: 6/27/1997
jamie: 12/18/1996
joanna: 12/6/1996

RBCC Red Blood Cell Collection

Full text data of LIFR