Loading…

ATM Gene Founder Haplotypes and Associated Mutations in Polish Families with Ataxia‐Telangiectasia

Summary Ataxia‐telangiectasia (A‐T) is an early onset autosomal recessive ataxia associated with characteristic chromosomal aberrations, cell cycle checkpoint defects, cancer susceptibility, and sensitivity to ionizing radiation. We utilized the protein truncation test (PTT), and single strand confo...

Full description

Saved in:
Bibliographic Details
Published in:Annals of human genetics 2005-11, Vol.69 (6), p.657-664
Main Authors: Mitui, M., Bernatowska, E., Pietrucha, B., Piotrowska‐Jastrzebska, J., Eng, L., Nahas, S., Teraoka, S., Sholty, G., Purayidom, A., Concannon, P., Gatti, R. A.
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Ataxia‐telangiectasia (A‐T) is an early onset autosomal recessive ataxia associated with characteristic chromosomal aberrations, cell cycle checkpoint defects, cancer susceptibility, and sensitivity to ionizing radiation. We utilized the protein truncation test (PTT), and single strand conformation polymorphism (SSCP) on cDNA, as well as denaturing high performance liquid chromatography (dHPLC) on genomic DNA (gDNA) to screen for mutations in 24 Polish A‐T families. Twenty‐six distinct Short Tandem Repeat (STR) haplotypes were identified. Three founder mutations accounted for 58% of the alleles. Three‐quarters of the families had at least one recurring (shared) mutation, which was somewhat surprising given the low frequency of consanguinity in Poland. STR haplotyping greatly improved the efficiency of mutation detection. We identified 44 of the expected 48 mutations (92%): sixty‐nine percent were nonsense mutations, 23% caused aberrant splicing, and 5% were missense mutations. Four mutations have not been previously described. Two of the Polish mutations have been observed previously in Amish and Mennonite A‐T patients; this is compatible with historical records. Shared mutations shared the same Single Nucleotide Polymorphism (SNP) and STR haplotypes, indicating common ancestries. The Mennonite mutation, 5932 G>T, is common in Russian A‐T families, and the STR haplovariants are the same in both Poland and Russia. Attempts to correlate phenotypes with genotypes were inconclusive due to the limited numbers of patients with identical mutations.
ISSN:0003-4800
1469-1809
DOI:10.1111/j.1529-8817.2005.00199.x