Autosomal recessive HEM/greenberg skeletal dysplasia is caused by 3 beta-hydroxysterol Delta(14)-reductase deficiency due to mutations in the lamin B receptor geneWaterham, HR., Koster, J., Mooyer, P., van Noort, G., Kelley, RI., Wilcox, WR., Hennekam, RCM. & Oosterwijk, JC., Apr-2003, In : American Journal of Human Genetics. 72, 4, p. 1013-1017 5 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||5|
|Journal||American Journal of Human Genetics|
|Publication status||Published - Apr-2003|
- LEMLI-OPITZ-SYNDROME, SACCHAROMYCES-CEREVISIAE, CHOLESTEROL-BIOSYNTHESIS, GREENBERG DYSPLASIA, REDUCTASE GENE, INBORN-ERRORS, EXPRESSION, DISORDER, HYDROPS, PRODUCE