Mutational spectrum of Smith–Lemli–Opitz syndrome

Authors

  • Hans R. Waterham,

    Corresponding author
    • Laboratory Genetic Metabolic Diseases (F0-222), Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
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    • Raoul C.M. Hennekam, M.D., Ph.D. is Professor of Pediatrics and Translational Genetics in Amsterdam and Professor of Clinical Genetics at the Institute of Neurology at University College London. He has been involved in SLOS ever since the late 1980s when he found variably elevated levels of lysosomal enzymes in several patients, to which Dr. John Opitz reacted to him in a letter that “this must be caused by a membrane abnormality and tell us something about the cause.”

  • Raoul C.M. Hennekam

    Corresponding author
    • Department of Pediatrics, H7-236, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
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    • Hans R. Waterham, Ph.D. is an Associate Professor and AMC Principal Investigator in the Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Paediatrics at the Academic Medical Center, Amsterdam, The Netherlands.


  • How to cite this article: Waterham HR, Hennekam RCM. 2012. Mutational spectrum of Smith–Lemli–Opitz syndrome. Am J Med Genet Part C Semin Med Genet 160C: 263–284.

Abstract

Smith–Lemli–Opitz syndrome (SLOS; OMIM #270400) is an autosomal recessive malformation syndrome characterized by a large spectrum of morphogenic and congenital anomalies. SLOS is caused by mutations in the DHCR7 gene, which encodes 7-dehydrocholesterol reductase, the enzyme that catalyzes the final step in cholesterol biosynthesis. We report on 154 currently known mutations in DHCR7 identified in patients affected with SLOS and discuss their coding consequences. These 154 mutations include 130 missense, 8 nonsense, 8 deletions, 2 insertions, 1 indel, and 5 splice site mutations. Using information available from published case reports and from patients identified in our clinical diagnostic laboratory, we analyzed correlations between genotype, clinical presentation and 7-dehydrocholesterol level. © 2012 Wiley Periodicals, Inc.

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