title: Mutation analysis of the ATM gene in two Chinese patients with ataxia telangiectasia.
abstract: Ataxia telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectasia, immunodeficiency, elevated alpha-fetoprotein level, chromosomal instability, predisposition to cancer, and radiation sensitivity. Although a lot of mutations in the ATM gene have been described, there is still no report about ATM mutations in Chinese population. Using a molecular approach, we screened for ATM mutations in two patients from two unrelated Chinese families. 100 normal controls were analyzed to exclude possibility of polymorphism. Two novel mutations in the ATM gene were identified. The first one is a novel, homozygous, 1346G>C (Gly449Ala) missense mutation. The second one is a compound heterozygous mutation, which consists of a novel, 610G>T (Gly204Stop) nonsense mutation, combined with a previously reported, 6679C>T (Arg2227Cys) missense mutation. The transversions 1346G>C (Gly449Ala) and 610G>T (Gly204Stop) are not localized either in the conserved PI-3 kinase domain or in the other domains of the ATM protein. The phenotypic features were characterized by progressive cerebellar ataxia, ocular telangiectasia, elevated alpha-fetoprotein level, immunodeficiency (agammaglo-bulinemia and T-cell defect), and rearrangements of chromosomes 7 and 14; brain MRI showed cerebellar atrophy, brain SPECT showed cerebellar regional cerebral blood flow (rCBF) hypoperfusion. To our knowledge, this is the first report of ATM mutations in Mainland China, in which the transversions 1346G>C (Gly449Ala) and 610G>T (Gly204Stop) are two novel, disease-causing mutations.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.forename: Jianguang
authors.initials: J
authors.lastname: Tang
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhao
authors.forename: Yuhu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Cai
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Long
authors.forename: Guo
authors.initials: G
authors.lastname: Wang
authors.forename: Heping
authors.initials: H
authors.lastname: Dai
mesh_terms: D000293:Adolescent; D000409:Alanine / Q000235:genetics; D044466:Asian People; D001260:Ataxia Telangiectasia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000409:Alanine; D005998:Glycine