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Am J Med Genet A. 2004 Apr 30;126A(3):272-7.

Slow progression of ataxia-telangiectasia with double missense and in frame splice mutations.

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1
Clinics of Obstetrics and Gynecology, Medical School Hannover, Hannover, Germany. doerk.thilo@mh-hannover.de

Abstract

Ataxia-telangiectasia (A-T) is caused by mutations of the ATM gene, the product of which is involved in the regulation of cellular responses to radiation damage. Ataxia usually starts in early childhood but a delayed age at onset and slower rate of neurological deterioration has been found for some patients with variant A-T. Only few patients have been documented to survive into the 4th decade. We report on a patient with an attenuated form of A-T who was diagnosed as having A-T by the age of 52 years and died by the age of 60 years. He was found to be a compound heterozygote for a double missense mutation (D2625E and A2626P) and a novel splicing mutation (496 + 5G --> A) of the ATM gene. Cytogenetic studies of the patient's lymphoblastoid cells revealed modest levels of bleomycin-induced chromosomal instability. Residual ATM protein was found at a level of 10-20% of wildtype. Low residual ATM kinase activity could be demonstrated towards p53, whereas it was poorly detectable towards nibrin. Our results corroborate the view that the clinical variability of A-T is partly determined by the mutation type and indicate that A-T can extend to late adulthood disease.

PMID:
15054841
DOI:
10.1002/ajmg.a.20601
[Indexed for MEDLINE]
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