Independent mutational events are rare in the ATM gene: Haplotype prescreening enhances mutation detection rate

Independent mutational events are rare in the ATM gene: Haplotype prescreening enhances mutation detection rate

Author Mitui, M. Google Scholar
Campbell, C. Google Scholar
Coutinho, G. Google Scholar
Sun, X Google Scholar
Lai, C. H. Google Scholar
Thorstenson, Y. Google Scholar
Castellvi-Bel, S. Google Scholar
Fernandez, L. Google Scholar
Monros, E. Google Scholar
Carvalho, BTC Google Scholar
Porras, O. Google Scholar
Fontan, G. Google Scholar
Gatti, R. A. Google Scholar
Institution David Geffen Sch Med
Universidade Federal do Rio de Janeiro (UFRJ)
Stanford Univ
Hosp St Joan de Deu
Universidade Federal de São Paulo (UNIFESP)
Natl Childrens Hosp Dr Carlos Saenz Herrera
Hosp La Paz
Abstract Mutations in the ATM gene are responsible for the autosomal recessive disorder ataxia,telangiectasia (A-T). Many different mutations have been identified using various techniques, with detection efficiencies ranging from 57 to 85%. in this study, we employed short tandem repeat (STR) haplotypes to enhance mutation identification in 55 unrelated A-T families of Iberian origin (20 Spanish, 17 Brazilian, and 18 Hispanic-American); we were able to identify 95% of the expected mutations. Allelic sizes were standardized based on a reference sample (CEPH 1347-2). Subsequent mutation screening was performed by PTT, SSCP, and DHPLC, and abnormal regions were sequenced. Many STR haplotypes were found within each population and six haplotypes were observed across several of these populations. Single nucleotide polymorphism (SNP) haplotypes further suggested that most of these common mutations are ancestrally related, and not hot spots. However, two mutations (8977C>T and 8264_8268delATAAG) may indeed be recurring mutational events. Common haplotypes were present in 13 of 20 Spanish A-T families (65%), in 11 of 17 Brazilian A-T families (65%), and, in contrast, in only eight of 18 Hispanic American families (44%). Three mutations were identified that would be missed by conventional screening strategies. in all, 62 different mutations (28 not previously reported) were identified and their associated haplotypes defined, thereby establishing a new database for Iberian A-T families, and extending the spectrum of worldwide ATM mutations. (C) 2003 Wiley-Liss, Inc.
Keywords ataxia-telangiectasia
masked mutations
haplotype prescreening
hot spots
mutation analysis
Language English
Date 2003-07-01
Published in Human Mutation. New York: Wiley-liss, v. 22, n. 1, p. 43-50, 2003.
ISSN 1059-7794 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 43-50
Access rights Closed access
Type Article
Web of Science ID WOS:000183965800005

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