Carrier frequency of the common mutation IVS8-1G>C in DHCR7 and estimate of the expected incidence of Smith-Lemli-Opitz syndrome

Kevin P. Battaile, Brian C. Battaile, Louise S. Merkens, Cheryl Maslen, Robert D. Steiner

    Research output: Contribution to journalArticle

    63 Citations (Scopus)

    Abstract

    Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomaly/mental retardation syndrome of variable severity with an incidence previously estimated at 1 in 20,000-60,000 based on case frequency surveys. Identification of the gene defect in SLOS has made it possible to calculate the carrier frequency and estimate disease incidence using molecular methods to identify carriers. Using a previously described PCR-RFLP assay we screened 1503 anonymous blood samples from random newborn screening blood spot cards for the presence of the common SLOS mutation IVS8-1G>C in order to determine the carrier frequency. Sixteen carriers were identified in the 1503 samples. Since the frequency of the IVS8-1G>C mutation among all SLOS gene mutations is known, the overall carrier frequency for all mutations can be calculated. The calculated carrier frequency for all mutations based on this result is 1 in 30, predicting an SLOS incidence of 1 in 1590 to 1 in 13,500. The current incidence estimate may, therefore, significantly underestimate the true incidence of SLOS. This discrepancy between calculated and observed incidence could be due to undiagnosed mild cases, misdiagnosed severe cases, death prior to diagnosis, or fetal loss. More comprehensive incidence studies are needed to determine if SLOS is as common as predicted by the very high (1 in 30) carrier frequency determined in this study.

    Original languageEnglish (US)
    Pages (from-to)67-71
    Number of pages5
    JournalMolecular Genetics and Metabolism
    Volume72
    Issue number1
    DOIs
    StatePublished - 2001

    Fingerprint

    Smith-Lemli-Opitz Syndrome
    Mutation Rate
    Blood
    Genes
    Incidence
    Assays
    Screening
    Defects
    Mutation
    Diagnostic Errors
    Intellectual Disability
    Restriction Fragment Length Polymorphisms
    Cohort Studies
    Polymerase Chain Reaction

    Keywords

    • Cholesterol
    • DHCR7
    • Metabolism
    • Population
    • Smith-Lemli-Opitz syndrome
    • Statistics

    ASJC Scopus subject areas

    • Biochemistry
    • Genetics
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Carrier frequency of the common mutation IVS8-1G>C in DHCR7 and estimate of the expected incidence of Smith-Lemli-Opitz syndrome. / Battaile, Kevin P.; Battaile, Brian C.; Merkens, Louise S.; Maslen, Cheryl; Steiner, Robert D.

    In: Molecular Genetics and Metabolism, Vol. 72, No. 1, 2001, p. 67-71.

    Research output: Contribution to journalArticle

    Battaile, Kevin P. ; Battaile, Brian C. ; Merkens, Louise S. ; Maslen, Cheryl ; Steiner, Robert D. / Carrier frequency of the common mutation IVS8-1G>C in DHCR7 and estimate of the expected incidence of Smith-Lemli-Opitz syndrome. In: Molecular Genetics and Metabolism. 2001 ; Vol. 72, No. 1. pp. 67-71.
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