[Research on clinical characteristics and ATM gene mutations in Chinese patients with ataxia-telangiectasia].
OBJECTIVE
To investigate the clinical manifestation and mutation characteristics of ATM gene in Chinese patients with ataxia-telangiectasia (AT).


METHODS
Sequence variants of the entire coding exons of ATM gene were tested using polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR), polyacrylamide gel electrophoresis (PAGE) and DNA direct sequencing in two Chinese patients clinically diagnosed as AT.


RESULTS
The clinical characteristics of two AT patients were progressive cerebellar ataxia with ages at onset of childhood, ocular-cutaneous telangiectasia and recurrent pulmonary infection due to immuno-deficiency; the serum alpha fetoprotein (AFP) levels were higher than normal, the serum immunoglobin IgA and IgG levels were lower than normal; brain MRI showed cerebellar atrophy, brain SPECT showed cerebellar regional cerebral blood flow (rCBF) hypoperfusion to a certain degree. Totally three nucleotide changes were identified. A missense mutation of G1346C in exon 11, which was a homozygotic mutation, was identified in one patient; a nonsense mutation of G610T in exon 6 combined with a missense mutation of C6679T in exon 47, which was a compound heterozygotic mutation, were identified in the other patient. They were co-segregated with the disease and were localized within the functional domain of ATM gene.


CONCLUSIONS
We have made gene diagnoses for two Chinese AT patients, in which three novel ATM gene mutations were identified.
Jiang
Hong
H
Department of Neurology, Xiangya Hospital, Central-south University, Changsha 410008, China.
Tang
Bei-sha
BS
Hu
Zheng-mao
ZM
Xia
Kun
K
Xu
Bo
B
Tang
Jian-guang
JG
D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
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