Clinical phenotype and genetic characteristics of ataxia - telangiectasia: four cases report

Objective To report 4 cases of ataxia-telangiectasia (AT) with ATM genetic mutation and to summarize the clinical and genetic characteristics of AT by literatures review. Methods Clinical data of 4 patients from 3 AT families was collected in detail and genomic DNA of the patients and family members was extracted from peripheral blood. Whole exon sequencing (WES) and polymerase chain reaction (PCR) of Sanger sequencing was used to analyse ATM genic mutation. Results Four patients were characterized by progressive cerebellar ataxia with onset in childhood, oculocutaneous telangiectasia, recurrent infection caused by immunodeficiency, α-fetoprotein (AFP) elevation and cerebellar atrophy shown in brain MRI were presented. Sequence analysis of ATM gene revealed two known compound heterozygous mutations c.8287C > T (p.Arg2763X) and c.9139C > T (p.Arg3047X) which were nonsense mutation in Case 1 and Case 2. In Case 3, there were two compound heterozygous mutations, including nonsence mutation c.8911C > T (p.Gln2971X) and deficit mutation c.7141_7151delAATGGAAAAAT (p.Asn2381GlufsX18) both of which were not reported previously. Case 4 carried homozygotic mutation c.1402_1403delAA (p. Lys468GlufsX18). Conclusions Four patients were diagnosed as AT with typical clinical manifestations. Patients with variant AT present mild nervous system symptom, normal head MRI and less involvement other than nervous systemt. Definite diagnosis should be dependant on ATM genetic testing. DOI: 10.3969/j.issn.1672-6731.2017.07.008