Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry†‡
James German
Weill Medical College of Cornell University, New York, New York
Search for more papers by this authorMaureen M. Sanz
Weill Medical College of Cornell University, New York, New York
Molloy College, Rockville Centre, New York
Search for more papers by this authorSusan Ciocci
Memorial Sloan-Kettering Cancer Center, New York, New York
Search for more papers by this authorTian Z. Ye
Memorial Sloan-Kettering Cancer Center, New York, New York
Search for more papers by this authorCorresponding Author
Nathan A. Ellis
Memorial Sloan-Kettering Cancer Center, New York, New York
Department of Medicine, University of Chicago, Chicago, Illinois
Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 4080, Chicago, IL 60637Search for more papers by this authorJames German
Weill Medical College of Cornell University, New York, New York
Search for more papers by this authorMaureen M. Sanz
Weill Medical College of Cornell University, New York, New York
Molloy College, Rockville Centre, New York
Search for more papers by this authorSusan Ciocci
Memorial Sloan-Kettering Cancer Center, New York, New York
Search for more papers by this authorTian Z. Ye
Memorial Sloan-Kettering Cancer Center, New York, New York
Search for more papers by this authorCorresponding Author
Nathan A. Ellis
Memorial Sloan-Kettering Cancer Center, New York, New York
Department of Medicine, University of Chicago, Chicago, Illinois
Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 4080, Chicago, IL 60637Search for more papers by this authorCommunicated by Albert de la Chapelle
This article is a US Government work, and, as such, is in the public domain in the United States of America.
Abstract
Bloom syndrome (BS) is caused by homozygous or compound heterozygous mutations in the RecQ DNA helicase gene BLM. Since the molecular isolation of BLM, characterization of BS-causing mutations has been carried out systematically using samples stored in the Bloom's Syndrome Registry. In a survey of 134 persons with BS from the Registry, 64 different mutations were identified in 125 of them, 54 that cause premature protein-translation termination and 10 missense mutations. In 102 of the 125 persons in whom at least one BLM mutation was identified, the mutation was recurrent, that is, it was shared by two or more persons with BS; 19 of the 64 different mutations were recurrent. Ethnic affiliations of the persons who carry recurrent mutations indicate that the majority of such persons inherit their BLM mutation identical-by-descent from a recent common ancestor, a founder. The presence of widespread founder mutations in persons with BS points to population genetic processes that repeatedly and pervasively generate mutations that recur in unrelated persons. Hum Mutat 28(8), 743–753, 2007. Published 2007 Wiley-Liss, Inc.
Supporting Information
The Supplementary Material referred to in this article can be accessed at http://www.interscience.wiley.com/jpages/1059-7794/suppmat
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