通过对钙蛋白酶3 mRNA的分析揭示的捷克LGMD2A患者的突变及其表型结果。

Mutations in Czech LGMD2A patients revealed by analysis of calpain3 mRNA and their phenotypic outcome.

作者信息

Chrobáková Tána, Hermanová Markéta, Kroupová Iva, Vondrácek Petr, Maríková Tat'ána, Mazanec Radim, Zámecník Josef, Stanek Jan, Havlová Miluse, Fajkusová Lenka

机构信息

Center of Molecular Biology and Gene Therapy, University Hospital Brno, Cernopolni 9, CZ-62500 Brno, Czech Republic.

出版信息

Neuromuscul Disord. 2004 Oct;14(10):659-65. doi: 10.1016/j.nmd.2004.05.005.

DOI:10.1016/j.nmd.2004.05.005

PMID:15351423

Abstract

Calpain3 (CAPN3, p94) is a muscle-specific nonlysosomal cysteine proteinase. Loss of proteolytic function or change of other properties of this enzyme (such as stability or ability to interact with other muscular proteins) is manifested as limb girdle muscular dystrophy type 2A (LGMD2A, calpainopathy). These pathological changes in properties of calpain3 are caused by mutations in the calpain3 gene. The fact that the human gene for calpain3 is quite long led us to analyse its coding sequence by reverse transcription-PCR followed by sequence analysis. This study reports nine mutations that we found by analysing mRNA of seven unrelated LGMD patients in the Czech Republic. Three of these mutations were novel, not described on the Leiden muscular dystrophy pages so far. Further, we observed a reduction of dysferlin in muscle membrane in five of our seven LGMD2A patients by immunohistochemical analysis of muscle sections.

摘要

钙蛋白酶3（CAPN3，p94）是一种肌肉特异性非溶酶体半胱氨酸蛋白酶。该酶蛋白水解功能丧失或其他特性改变（如稳定性或与其他肌肉蛋白相互作用的能力）表现为2A型肢带型肌营养不良症（LGMD2A，钙蛋白酶病）。钙蛋白酶3特性的这些病理变化是由钙蛋白酶3基因突变引起的。由于人类钙蛋白酶3基因相当长，我们通过逆转录聚合酶链反应（RT-PCR）随后进行序列分析来分析其编码序列。本研究报告了我们通过分析捷克共和国7名无关LGMD患者的mRNA发现的9个突变。其中3个突变是新发现的，迄今为止在莱顿肌营养不良症网页上尚未描述。此外，通过对肌肉切片进行免疫组织化学分析，我们在7名LGMD2A患者中的5名患者中观察到肌膜中肌营养不良蛋白减少。