You are here

Article Text

Article menu
Download PDFPDF
Electronic letters
Smith-Lemli-Opitz syndrome: carrier frequency and spectrum of DHCR7 mutations in Canada
  1. J S Waye1,2,
  2. L M Nakamura3,
  3. B Eng1,
  4. L Hunnisett1,2,
  5. D Chitayat4,
  6. T Costa5,
  7. M J M Nowaczyk1,2,6
  1. 1Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada
  2. 2Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  3. 3Department of Biology, McMaster University, Hamilton, Ontario, Canada
  4. 4Toronto Hospital, Toronto, Ontario, Canada
  5. 5IWK Health Centre, Halifax, Nova Scotia, Canada
  6. 6Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to:
 Dr M J M Nowaczyk, Room 3N16, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4J9;
 nowaczyk{at}hhsc.ca

https://doi.org/10.1136/jmg.39.6.e31

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Smith-Lemli-Opitz syndrome (SLOS, OMIM 270400) is an autosomal recessive disorder of cholesterol biosynthesis resulting from deficient 3β-hydroxysterol Δ7-reductase (DHCR7) activity.1,2 Patients with SLOS have a characteristic facial phenotype, various degrees of cleft palate and of syndactyly of toes 2 and 3, failure to thrive, behavioural problems, and mental retardation in addition to variable combinations of external and internal malformations.3–5 The spectrum of severity extends from prenatal death with holoprosencephaly or other lethal malformations to minimally physically affected patients with normal intelligence or minimal intellectual impairment. Most patients with SLOS have abnormally low levels of plasma cholesterol and all have raised levels of its immediate precursor, 7-dehydrocholesterol (7DHC).2

    The DHCR7 gene has been mapped to chromosome 11q13, spans approximately 14 kb, and encodes a protein of 475 amino acid residues.6 To date, 85 different DHCR7 mutations have been identified in more than 200 SLOS patients.5,7,8 Missense mutations comprise over 85% of the known alleles, although the two most common alleles are a splice acceptor site mutation (IVS8-1G→C) and a nonsense mutation (W151X).

    SLOS is most common among people of European descent, with estimated incidences ranging from 1 in 10 000 to 1 in 60 000 depending on the diagnostic criteria and the reference population.5 Several groups have shown that the carrier rate for the most common mutation, IVS8-1G→C, is approximately 1 in 100 for white populations in North America, and even higher in some European populations.9–12 Haplotypes of DHCR7 single nucleotide polymorphisms (SNPs) have been used to investigate the origin and distribution patterns of SLOS mutations in different populations, showing both founder effects and recurrent mutations.13

    In this report, we summarise our molecular diagnostic experiences with SLOS in Canada. DHCR7 mutations and SNPs were identified in …

    View Full Text