杨灿,金皎
YANG Can,JIN Jiao

• 1:贵州医科大学附属医院儿科血液专科
• 2:贵州医科大学临床医学院

摘要(Abstract)：

目的 探讨眼-脑-肝-肾综合征(COACH综合征)的临床及家系特点。方法 以1例COACH综合征患者(先证者)及其3代内家系成员作为研究对象，收集先证者的临床资料[包括病史、体格检查、肝功能、肝脏弹力纤维检测、眼部学相干断层成像(OCT)检查、颅脑磁共振成像(MRI)检查等]及其3代内家系成员的病史及体格检查，分别取先证者及其3代内家系成员外周血各2 mL,采用全外显子组捕获测序技术进行基因测序。结果 先证者有智力发育落后、并趾畸形、先天性肝纤维化(CHF)、眼部视网膜外层结构缺损，MRI呈现典型的“磨牙征”和“蝙蝠征”;先证者大舅幼年发热后出现智力发育落后，余家属无类似症状；基因测序检测出先证者8号染色体跨膜蛋白67基因(TMEM67)c.725A>G(p.N242S)和c.1288+1G>A(splicing)双重杂合突变，其中c.725A>G(p.N242S)突变为父系遗传、为已有报道的突变，c.1288+1G>A(splicing)突变为母系遗传、为新发现的致病突变。结论 确诊患儿为COACH综合征，并诊断其家系遗传特点为常染色体隐性遗传，同时检测出COACH综合征新TMEM67突变位点。
Objective To explore the clinical features and family characteristics of eye-brain-liver-kidney syndrome(COACH syndrome). Methods A patient with clinically considered COACH syndrome(proband) and his family members within three generations were taken as the research objects. The clinical data(including medical history, physical examination, liver function, liver elastic fiber test, eye OCT examination, and brain MRI examination) and family data(including medical history and physical examination) were collected. 2 mL of peripheral blood were taken from the proband and his family within three generations, and the whole exome capture sequencing technology was used to sequence the proband and his family. Results The proband was featured with mental retardation, syndactyly, congenital hepatic fibrosis(CHF), retina coloboma, and 'molar tooth sign' and 'bat sign' on MRI. The proband's uncle developed mental retardation after childhood fever, and the rest of his family members had no similar symptoms. Gene sequencing detected a compound heterozygous mutations of c.725 A>G(p.N242 S) and c.1288+1 G>A(splicing) in the transmembrane protein 67 gene(TMEM67) on chromosome 8. The c.725 A>G(p.N242 S) mutation was known and paternally inherited, and the c.1288+1 G>A(splicing) mutation was maternally inherited which was a novel pathogenic mutation. Conclusions The child is diagnosed as COACH syndrome, the genetic characteristics of his family are autosomal recessive inheritance, and the novel TMEM67 mutation site of COACH syndrome is detected.

关键词(KeyWords)： 纤毛病;COACH综合征;TMEM67基因突变;磨牙征;先天性肝纤维化;眼部结构缺失;智力发育落后
ciliopathies;COACH syndrome;TMEM67 gene mutation;molar tooth sign;congenital hepatic fibrosis(CHF);coloboma;mental retardation

Abstract:

Keywords:

基金项目(Foundation): 贵州省科技计划项目(黔科合平台人才[2019]5406);; 贵州省卫生健康委科学技术基金(gzwjkj2019-1-002)

作者(Author): 杨灿,金皎
YANG Can,JIN Jiao

DOI: 10.19367/j.cnki.2096-8388.2022.12.015

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