不稳定临界GAA三联体重复等位基因携带者的弗里德赖希共济失调

Friedreich ataxia in carriers of unstable borderline GAA triplet-repeat alleles.

作者信息

Sharma Rajesh, De Biase Irene, Gómez Mariluz, Delatycki Martin B, Ashizawa Tetsuo, Bidichandani Sanjay I

机构信息

Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

出版信息

Ann Neurol. 2004 Dec;56(6):898-901. doi: 10.1002/ana.20333.

DOI:10.1002/ana.20333

PMID:15562408

Abstract

Friedreich ataxia patients are homozygous for expanded GAA triplet-repeats containing 66 to 1,700 triplets. We report two patients with delayed-onset, hyperreflexia and gradually progressive disease. Both were heterozygous for large expansions and also carried alleles with 44 and 66 triplet-repeats, respectively. Due to somatic instability, 15% (GAA-44) and 75% (GAA-66) of cells contained alleles with >/=66 triplet-repeats, constituting a plausible mechanism for their mild phenotype. A sibling with a stable GAA-37 allele and a large expansion was clinically normal. Instability of borderline alleles confers a risk for Friedreich ataxia, and the range of pathogenic alleles is broader than previously recognized.

摘要

弗里德赖希共济失调患者为纯合子，其GAA三联体重复序列扩增，包含66至1700个三联体。我们报告了两名发病延迟、反射亢进且疾病逐渐进展的患者。两人均为大扩增的杂合子，分别还携带44和66个三联体重复序列的等位基因。由于体细胞不稳定性，15%（GAA - 44）和75%（GAA - 66）的细胞含有≥66个三联体重复序列的等位基因，这构成了其轻度表型的一种合理机制。一名携带稳定的GAA - 37等位基因且有大扩增的同胞临床正常。临界等位基因的不稳定性会带来弗里德赖希共济失调风险，且致病等位基因的范围比之前认识的更广。