Novel mutations in ataxia telangiectasia and AOA2 associated with prolonged survival

JOURNAL OF THE NEUROLOGICAL SCIENCES

卷:335

Article

Davis, Marie Y.¹  Keene, C. Dirk²  Swanson, Phillip D.¹  Sheehy, Conor³  Bird, Thomas D.¹ 

[1] Univ Washington, Dept Neurol, Seattle, WA 98195 USA

[2] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

[3] Oregon Hlth & Sci Univ, Div Pulm & Crit Care, Portland, OR USA

关键词: Ataxia;    Ataxia telangiectasia;    AT;    Ataxia oculomotor apraxia type 2;    AOA2;    Senataxin;    SETX;    ATM;   

DOI  :  10.1016/j.jns.2013.09.014

来源: Elsevier

【 摘 要 】

Ataxia telangiectasia (AT) and ataxia oculomotor apraxia type 2 (AOA2) are autosomal recessive ataxias caused by mutations in genes involved in maintaining DNA integrity. Lifespan in AT is greatly shortened (20s-30s) due to increased susceptibility to malignancies (leukemia/lymphoma). Lifespan in AOA2 is uncertain. We describe a woman with variant AT with two novel mutations in ATM (IVS14 + 2 T> G and 5825C > T, p.A1942V) who died at age 48 with pancreatic adenocarcinoma. Her mutations are associated with an unusually long life for AT and with a cancer rarely associated with that disease. We also describe two siblings with AOA2, heterozygous for two novel mutations in senataxin (3 bp deletion c.343-345 and 1398 T> G, p.I466M) who have survived into their 70s, allowing us to characterize the longitudinal course of AOA2. In contrast to AT, we show that persons with AOA2 can experience a prolonged lifespan with considerable motor disability. Published by Elsevier B.V.

【 授权许可】

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