当前位置： SCI文献检索 > NEUROLOGY期刊下所有文献 > Clinical spectrum of ataxia-telangiectasia in adulthood.

Clinical spectrum of ataxia-telangiectasia in adulthood.

Abstract：

OBJECTIVE:To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. METHODS:Retrospective analysis of the clinical characteristics and course of disease in 13 adult patients with variant A-T of 9 families and 6 unrelated adults with classic A-T and mutation analysis of the ATM gene and measurements of ATM protein expression and kinase activity. RESULTS:Patients with variant A-T were only correctly diagnosed in adulthood. They often presented with extrapyramidal symptoms in childhood, whereas cerebellar ataxia appeared later. Four patients with variant A-T developed a malignancy. Patients with classic and variant A-T had elevated serum alpha-fetoprotein levels and chromosome 7/14 rearrangements. The mildest variant A-T phenotype was associated with missense mutations in the ATM gene that resulted in expression of some residual ATM protein with kinase activity. Two splicing mutations, c.331 + 5G>A and c.496 + 5G>A, caused a more severe variant A-T phenotype. The splicing mutation c.331 + 5G>A resulted in less ATM protein and kinase activity than the missense mutations. CONCLUSIONS:Ataxia-telangiectasia (A-T) should be considered in patients with unexplained extrapyramidal symptoms. Early diagnosis is important given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment. Measurement of serum alpha-fetoprotein and chromosomal instability precipitates the correct diagnosis. There is a clear genotype-phenotype relation for A-T, since the severity of the phenotype depends on the amount of residual kinase activity as determined by the genotype.

journal_name

Neurology

journal_title

Neurology

authors

Verhagen MM,Abdo WF,Willemsen MA,Hogervorst FB,Smeets DF,Hiel JA,Brunt ER,van Rijn MA,Majoor Krakauer D,Oldenburg RA,Broeks A,Last JI,van't Veer LJ,Tijssen MA,Dubois AM,Kremer HP,Weemaes CM,Taylor AM,van Deuren M

doi

10.1212/WNL.0b013e3181af33bd

subject

Has Abstract

pub_date

2009-08-11 00:00:00

pages

430-7

issue

eissn

0028-3878

issn

1526-632X

pii

WNL.0b013e3181af33bd

journal_volume

pub_type

杂志文章

在线工具

Clinical spectrum of ataxia-telangiectasia in adulthood.