Rapid and efficient ATM mutation detection by fluorescent chemical cleavage of mismatch: identification of four novel mutations

Citation
L. Izatt et al., Rapid and efficient ATM mutation detection by fluorescent chemical cleavage of mismatch: identification of four novel mutations, EUR J HUM G, 7(3), 1999, pp. 310-320
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
EUROPEAN JOURNAL OF HUMAN GENETICS
ISSN journal
1018-4813 → ACNP
Volume
7
Issue
3
Year of publication
1999
Pages
310 - 320
Database
ISI
SICI code
1018-4813(199904)7:3<310:RAEAMD>2.0.ZU;2-7
Abstract
Mutations in the Ataxia Telangiectasia Mutated (ATM) gene are responsible f or the autosomal recessive disease Ataxia Telangiectasia (A-T). A wide vari ety of mutations scattered across the entire coding region (9168 bp) of ATM have been found, which presents a challenge in developing an efficient mut ation screening strategy for detecting unknown mutations, Fluorescent chemi cal cleavage of mismatch (FCCM) is an ideal mutation screening method, offe ring a non-radioactive alternative to other techniques such as restriction endonuclease fingerprinting (REF), Using FCCM, we have developed an efficie nt, accurate and sensitive mutation detection method for screening RT-PCR p roducts for ATM mutations. We have identified seven ATM mutations in five A -T families, four of which are previously unknown, We quantified ATM protei n expression in four of the families and found variable ATM protein express ion (0-6.4%), further evidence for mutant ATM protein expression in both cl assic and variant A-T patients. We conclude that FCCM offers a robust ATM m utation detection method and can be used to screen for ATM mutations in can cer-prone populations.