PMID- 12618959
OWN - NLM
STAT- MEDLINE
DCOM- 20030505
LR  - 20231213
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 72
IP  - 4
DP  - 2003 Apr
TI  - Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3 
      beta-hydroxysterol delta 14-reductase deficiency due to mutations in the lamin B 
      receptor gene.
PG  - 1013-7
AB  - Hydrops-ectopic calcification-"moth-eaten" (HEM) or Greenberg skeletal dysplasia 
      is an autosomal recessive chondrodystrophy with a lethal course, characterized by 
      fetal hydrops, short limbs, and abnormal chondro-osseous calcification. We found 
      elevated levels of cholesta-8,14-dien-3beta-ol in cultured skin fibroblasts of an 
      18-wk-old fetus with HEM, compatible with a deficiency of the cholesterol 
      biosynthetic enzyme 3beta-hydroxysterol delta(14)-reductase. Sequence analysis of 
      two candidate genes encoding putative human sterol delta(14)-reductases (TM7SF2 
      and LBR) identified a homozygous 1599-1605TCTTCTA-->CTAGAAG substitution in exon 
      13 of the LBR gene encoding the lamin B receptor, which results in a truncated 
      protein. Functional complementation of the HEM cells by transfection with control 
      LBR cDNA confirmed that LBR encoded the defective sterol delta(14)-reductase. 
      Mutations in LBR recently have been reported also to cause Pelger-Huet anomaly, 
      an autosomal dominant trait characterized by hypolobulated nuclei and abnormal 
      chromatin structure in granulocytes. The fact that the healthy mother of the 
      fetus showed hypolobulated nuclei in 60% of her granulocytes confirms that 
      classic Pelger-Huet anomaly represents the heterozygous state of 
      3beta-hydroxysterol delta(14)-reductase deficiency.
FAU - Waterham, Hans R
AU  - Waterham HR
AD  - Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, 
      Amsterdam, The Netherlands. h.r.waterham@amc.uva.nl
FAU - Koster, Janet
AU  - Koster J
FAU - Mooyer, Petra
AU  - Mooyer P
FAU - Noort Gv, Gerard van
AU  - Noort Gv Gv
FAU - Kelley, Richard I
AU  - Kelley RI
FAU - Wilcox, William R
AU  - Wilcox WR
FAU - Wanders, Ronald J A
AU  - Wanders RJ
FAU - Hennekam, Raoul C M
AU  - Hennekam RC
FAU - Oosterwijk, Jan C
AU  - Oosterwijk JC
LA  - eng
SI  - GENBANK/AF096303
SI  - GENBANK/L25931
SI  - GENBANK/L25932
SI  - GENBANK/L25933
SI  - GENBANK/L25934
SI  - GENBANK/L25935
SI  - GENBANK/L25936
SI  - GENBANK/L25937
SI  - GENBANK/L25938
SI  - GENBANK/L25939
SI  - GENBANK/L25940
SI  - GENBANK/L25941
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030228
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (DNA Primers)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.3.1.70 (delta(14)-sterol reductase)
SB  - IM
MH  - Base Sequence
MH  - Bone Diseases/*genetics/pathology
MH  - Cholesterol/biosynthesis
MH  - DNA Primers
MH  - *Genes, Recessive
MH  - Humans
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Oxidoreductases/deficiency/*genetics
MH  - Receptors, Cytoplasmic and Nuclear/*genetics
MH  - Sequence Analysis, DNA
MH  - Lamin B Receptor
PMC - PMC1180330
EDAT- 2003/03/06 04:00
MHDA- 2003/05/06 05:00
PMCR- 2003/10/01
CRDT- 2003/03/06 04:00
PHST- 2002/11/15 00:00 [received]
PHST- 2002/12/26 00:00 [accepted]
PHST- 2003/03/06 04:00 [pubmed]
PHST- 2003/05/06 05:00 [medline]
PHST- 2003/03/06 04:00 [entrez]
PHST- 2003/10/01 00:00 [pmc-release]
AID - S0002-9297(07)60622-3 [pii]
AID - 024716 [pii]
AID - 10.1086/373938 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2003 Apr;72(4):1013-7. doi: 10.1086/373938. Epub 2003 Feb 28.