患有新型FANCA和ATM无效突变独特组合的同胞中的范可尼贫血和共济失调毛细血管扩张症。

Fanconi Anemia and Ataxia Telangiectasia in Siblings who Inherited Unique Combinations of Novel FANCA and ATM Null Mutations.

作者信息

Balta Gunay, Patiroglu Turkan, Gumruk Fatma

机构信息

Department of Pediatrics, Division of Pediatric Hematology, Faculty of Medicine, Hacettepe University, Ankara.

Department of Pediatrics, Division of Pediatric Hematology, Faculty of Medicine, Erciyes University, Kayseri, Turkey.

出版信息

J Pediatr Hematol Oncol. 2019 Apr;41(3):243-246. doi: 10.1097/MPH.0000000000001336.

DOI:10.1097/MPH.0000000000001336

PMID:30339652

Abstract

A unique consanguineous family with 2 genomic instability disorders, Fanconi anemia and ataxia telangiectasia, revealed exceptional combinations of null mutations in the FANCA and ATM genes. Two siblings with Fanconi anemia had novel homozygous consecutive microdeletions (c.1361-1370delCCTCCTTTGG, c.1374delC) adjoined to upstream 65 nucleotide direct tandem repeats and deletion hotspot motifs in the FANCA gene. The sibling with ataxia telangiectasia revealed a homozygous p.Arg2993Stop (c.8977C>T) null mutation in the ATM gene. All patients were also heterozygous for the opposite mutations without any additional clinical or laboratory manifestations. Double heterozygote parents did not present any clinical symptoms suggestive of the 2 disorders.

摘要

一个独特的近亲家族患有两种基因组不稳定疾病，即范可尼贫血和共济失调毛细血管扩张症，该家族显示出FANCA和ATM基因纯合突变的特殊组合。两名患有范可尼贫血的兄弟姐妹在FANCA基因中出现了新的纯合连续微缺失（c.1361 - 1370delCCTCCTTTGG，c.1374delC），毗邻上游65个核苷酸的直接串联重复序列和缺失热点基序。患有共济失调毛细血管扩张症的兄弟姐妹在ATM基因中显示出纯合的p.Arg2993Stop（c.8977C>T）无义突变。所有患者对于相反的突变也是杂合子，且没有任何额外的临床或实验室表现。双杂合子父母未表现出任何提示这两种疾病的临床症状。