MYH9相关综合征家系临床和基因突变分析

Clinical manifestations and gene mutations of a Chinese family with MYH9-related syndrome

摘要:

目的：对MYH9相关综合征家系进行临床表现和相关致病基因分析，探讨其早期诊断的方法和发病机制。方法：对一个MYH9相关综合征家系3名患者及家族3代共11人进行外周血检查，采用PCR扩增、DNA直接测序技术进行MYH9基因突变分析。同时进行100名健康对照人群的MYH9基因检测。结果：外周血检测发现家系患者血小板减少，血小板体积增大，中性粒细胞中有包涵体。基因检测经PCR-DNA直接测序在先证者MYH9基因第30号外显子发现了碱基G/A错义突变，该突变导致GAC编码的第1424位天冬酰胺（D）突变为AAC编码的天冬氨酸（N），即D1424N突变。家系中患者检出与先证者相同的突变，而家系内健康人和家系外100名健康对照未发现这种突变。结论：MYH9相关综合征患者临床表现不一。MYH9基因突变是该综合征的分子发病机制，D1424N突变是国内未曾报道过的新突变。MYH9相关综合征的早期诊断有赖于家系调查和相关检查的早期开展。

Abstract:

OBJECTIVE: To explore the method for early diagnosis and pathogenesis of MYH9-related syndrome through analysis of the clinical manifestation and gene mutation of a Chinese family with MYH9-related syndrome. METHODS: Peripheral blood samples were collected from a three-generation Chinese family with MYH9-relatedsyndrome (11 individuals, including 3 patients) and 100 healthy individuals. Polymerase chain reaction (PCR) amplification and direct sequencing of DNA were performed to analyze mutations of MYH9 gene. RESULTS: Thrombocytopenia, increased volume of platelet, and granulocyte inclusion bodies were found in the patients with MYH9-related syndrome via a peripheral blood test. A missense mutation of a base pair (G-A) in exon 30 was revealed by PCR amplification and direct sequencing of MYH9 of the proband. That lead to Asp-Asn substitution at position 1424 (D1424N mutation). The mutation was the same as in other patients with MYH9-related syndrome. It was not found in healthy people from the Chinese family or in the other 100 healthy individuals. CONCLUSIONS: Patients with MYH9-related syndrome show diverse symptoms. Mutation of MYH9 gene may be the molecular mechanism of MYH9-related syndrome, and D1424N mutation of MYH9 has not been reported in Chinese people. Early diagnosis of MYH9-related syndrome can be carried out by investigating family history and making early examinations.