Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Abnormal sterol metabolism in patients with Conradi‐Hünermann‐Happle syndrome and sporadic lethal chondrodysplasia punctata

Abnormal sterol metabolism in patients with Conradi‐Hünermann‐Happle syndrome and sporadic lethal... The term, “chondrodysplasia punctata” (CDP) denotes a pattern of abnormal punctate calcification of dystrophic epiphyseal cartilage and certain other cartilaginous structures, such as the larynx. CDP occurs in a variety of genetic disorders associated with skeletal dwarfism and can also be caused by prenatal exposure to warfarin. Although the most studied clinical syndrome with CDP, rhizomelic chondrodysplasia punctata (RCDP), is known to be caused by several different abnormalities of plasmalogen biosynthesis, there are many other genetic disorders with CDP for which the biochemical cause is unknown. Because patients with Smith‐Lemli‐Opitz syndrome, a primary disorder of sterol biosynthesis, often have rhizomesomelic limb shortness and, less commonly, CDP, we assessed sterol levels and metabolism in patients with different clinical forms of CDP. By quantitative sterol analysis of a variety of tissues, we identified 5 patients with similar radiological findings and abnormally increased levels of 8‐dehydrocholesterol and cholest‐8(9)‐en‐3β‐ol, suggesting a deficiency of 3β‐hydroxysteroid‐Δ8,Δ7‐isomerase, a principal enzyme of cholesterol biosynthesis. Cultured cells available from one patient showed increased levels of the same two sterols, decreased synthesis of cholesterol, and a pattern of inhibition by triparanol and AY‐9944 consistent with a deficiency of 3β‐hydroxysteroid‐Δ8,Δ7‐isomerase. Clinical diagnoses among the 5 patients included X‐linked dominant Conradi‐Hünermann‐Happle syndrome and nonspecific lethal CDP. We conclude that abnormal cholesterol biosynthesis is a characteristic of some clinical syndromes with rhizomesomelic dwarfing and CDP. Am. J. Med. Genet. 83:213–219, 1999. © 1999 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Medical Genetics Part A Wiley

Abnormal sterol metabolism in patients with Conradi‐Hünermann‐Happle syndrome and sporadic lethal chondrodysplasia punctata

Download PDF
7 pages

Loading next page...
 
/lp/wiley/abnormal-sterol-metabolism-in-patients-with-conradi-h-nermann-happle-XHEWYzEkK4

References (40)

Publisher
Wiley
Copyright
Copyright © 1999 Wiley Subscription Services, Inc., A Wiley Company
ISSN
1552-4825
eISSN
1552-4833
DOI
10.1002/(SICI)1096-8628(19990319)83:3<213::AID-AJMG15>3.0.CO;2-C
Publisher site
See Article on Publisher Site

Abstract

The term, “chondrodysplasia punctata” (CDP) denotes a pattern of abnormal punctate calcification of dystrophic epiphyseal cartilage and certain other cartilaginous structures, such as the larynx. CDP occurs in a variety of genetic disorders associated with skeletal dwarfism and can also be caused by prenatal exposure to warfarin. Although the most studied clinical syndrome with CDP, rhizomelic chondrodysplasia punctata (RCDP), is known to be caused by several different abnormalities of plasmalogen biosynthesis, there are many other genetic disorders with CDP for which the biochemical cause is unknown. Because patients with Smith‐Lemli‐Opitz syndrome, a primary disorder of sterol biosynthesis, often have rhizomesomelic limb shortness and, less commonly, CDP, we assessed sterol levels and metabolism in patients with different clinical forms of CDP. By quantitative sterol analysis of a variety of tissues, we identified 5 patients with similar radiological findings and abnormally increased levels of 8‐dehydrocholesterol and cholest‐8(9)‐en‐3β‐ol, suggesting a deficiency of 3β‐hydroxysteroid‐Δ8,Δ7‐isomerase, a principal enzyme of cholesterol biosynthesis. Cultured cells available from one patient showed increased levels of the same two sterols, decreased synthesis of cholesterol, and a pattern of inhibition by triparanol and AY‐9944 consistent with a deficiency of 3β‐hydroxysteroid‐Δ8,Δ7‐isomerase. Clinical diagnoses among the 5 patients included X‐linked dominant Conradi‐Hünermann‐Happle syndrome and nonspecific lethal CDP. We conclude that abnormal cholesterol biosynthesis is a characteristic of some clinical syndromes with rhizomesomelic dwarfing and CDP. Am. J. Med. Genet. 83:213–219, 1999. © 1999 Wiley‐Liss, Inc.

Journal

American Journal of Medical Genetics Part A – Wiley

Published: Jul 19, 2000

Keywords: ; ;

There are no references for this article.