| DHCR7 mutation carrier rates and prevalence of the RSH/Smith-Lemli-Opitz syndrome: where are the patients? | |
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MedLine Citation:
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PMID: 16906538 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RSH/Smith-Lemli-Opitz (SLOS) is an inborn error of metabolism with protean manifestations. Its exact incidence and prevalence are not known; however, the carrier rate for the most frequently occurring mutation, the null mutation IVS8-1G > C, is approximately 1 in 100 for the Caucasian population in North America (1%) and possibly as high as 1 in 50 to 1 in 30 in Central European populations (2-3.3%). Based on the allele frequencies and the proportion of this mutation observed in various patient populations, the expected incidence of RSH/SLOS in those populations was calculated and reported to be between 1 in 1,590 and 1 in 17,000. However, around the world the observed prevalence and incidence are much lower than those calculated from the individual mutation carrier rates observed in any given population. The discrepancy between the expected incidence and prevalence can be explained only in part by the neonatal and infancy deaths of the most severely affected children with RSH/SLOS and the under ascertainment of mild and atypical cases at the mild end of the spectrum. RSH/SLOS may be responsible for a high number of miscarriages. Recent observations estimate the prevalence of SLOS at 16 weeks of gestation as similar to that observed at birth (approximately 1 in 60,000) suggesting that either reduced fertility of carrier couples or losses of affected embryos or fetuses in the first trimester play a significant role in reducing the second trimester prevalence of RSH/SLOS. It is possible that the estimates of carrier rates based on population screening for the most commonly occurring mutations may not reflect the true carrier rates in the population. In order to reconcile the above-mentioned paradoxes, we propose a model based on a higher than observed carrier frequency of the most common mutation and on very high fetal loss of homozygotes for that mutation. |
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Authors:
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Małgorzata J M Nowaczyk; John S Waye; James D Douketis |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: American journal of medical genetics. Part A Volume: 140 ISSN: 1552-4825 ISO Abbreviation: Am. J. Med. Genet. A Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-28 Completed Date: 2006-11-29 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101235741 Medline TA: Am J Med Genet A Country: United States |
Other Details:
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Languages: eng Pagination: 2057-62 Citation Subset: IM |
Affiliation:
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Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada. nowaczyk@hhsc.ca |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Canada
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epidemiology Female Fetal Death / epidemiology, genetics Gene Frequency Heterozygote Homozygote Humans Infant Infant, Newborn Male Models, Genetic Mutation* Oxidoreductases Acting on CH-CH Group Donors / deficiency, genetics* Pregnancy Prenatal Diagnosis Smith-Lemli-Opitz Syndrome / enzymology*, epidemiology, genetics* |
| Chemical | |
Reg. No./Substance:
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EC 1.3.-/Oxidoreductases Acting on CH-CH Group Donors; EC 1.3.1.21/7-dehydrocholesterol reductase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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