亨廷顿基因（CAG）n重复序列的有限扩增：一种前突变（？）

Limited expansion of the (CAG)n repeat of the Huntington gene: a premutation (?).

作者信息

Legius E, Cuppens H, Dierick H, Van Zandt K, Dom R, Fryns J P, Evers-Kiebooms G, Decruyenaere M, Demyttenaere K, Marynen P

机构信息

Center for Human Genetics, University of Leuven, Belgium.

出版信息

Eur J Hum Genet. 1994;2(1):44-50. doi: 10.1159/000472340.

DOI:10.1159/000472340

PMID:8044653

Abstract

Huntington's disease (HD) is an autosomal dominant disorder with choreic movements, psychiatric manifestations and cognitive dysfunction. Recently the IT15 gene on chromosome 4p has been identified containing an unstable and expanded trinucleotide repeat in patients with HD. We report on the characteristics of this repeat in 248 individuals from 41 Belgian HD families. The length of the expanded repeat was defined precisely and reproducibly on an ALF sequencer and correlated well with the age of onset (r = -0.72). Paternal transmission of the expanded repeat resulted on average in a significantly longer repeat length (+2.79 repeats) than maternal transmission (-0.29 repeats). (CAG)n repeat of a premutation (?) size was observed in this population with subsequent expansion in the disease range. Presymptomatic or prenatal testing using only linked markers may be problematic in these cases.

摘要

亨廷顿舞蹈症（HD）是一种常染色体显性疾病，伴有舞蹈样动作、精神症状和认知功能障碍。最近，已确定4号染色体短臂上的IT15基因在HD患者中含有不稳定且扩展的三核苷酸重复序列。我们报告了来自41个比利时HD家族的248名个体中该重复序列的特征。在ALF测序仪上精确且可重复地确定了扩展重复序列的长度，并且该长度与发病年龄密切相关（r = -0.72）。扩展重复序列的父系传递平均导致的重复序列长度（+2.79个重复序列）显著长于母系传递（-0.29个重复序列）。在该人群中观察到了处于前突变（？）大小的（CAG）n重复序列，随后在疾病范围内发生了扩展。在这些病例中，仅使用连锁标记进行症状前或产前检测可能存在问题。