纯合的GJA1基因突变导致哈勒曼-施特雷夫/眼齿指综合征谱系表型。

A homozygous GJA1 gene mutation causes a Hallermann-Streiff/ODDD spectrum phenotype.

作者信息

Pizzuti Antonio, Flex Elisabetta, Mingarelli Rita, Salpietro Carmelo, Zelante Leopoldo, Dallapiccola Bruno

机构信息

Ospedale Casa Sollievo della Sofferenza and Istituto CSS-Mendel, Roma, Italy.

出版信息

Hum Mutat. 2004 Mar;23(3):286. doi: 10.1002/humu.9220.

DOI:10.1002/humu.9220

PMID:14974090

Abstract

Oculodentodigital dysplasia (ODDD) and Hallermann-Streiff syndrome (HSS) share several clinical characteristics. However, while ODDD is a dominantly inherited disorder due to mutations in the connexin 43 gene GJA1, the inheritance pattern of the HSS syndrome is still debated. Overlapping phenotypes have been described. In one of such cases we found a homozygous change at the very conserved R76 codon (c.227G>A, p.R76H), the clinically normal parents being heterozigous carriers of the same mutation. A different base change at the same codon (p.R76S) leads to a complete dominant ODDD phenotype. A case of full-blown HSS phenotype was also analysed but GJA1 mutations were not found. GJA1 homozygous hypomorphic mutations can result in a phenotype in the HSS/ODDD spectrum.

摘要

眼牙指发育不全（ODDD）和哈勒曼-施特雷夫综合征（HSS）有若干共同的临床特征。然而，ODDD是一种因连接蛋白43基因GJA1发生突变而导致的显性遗传疾病，而HSS综合征的遗传模式仍存在争议。已有重叠表型的描述。在其中一个此类病例中，我们在高度保守的R76密码子处发现了一个纯合变化（c.227G>A，p.R76H），临床正常的父母是同一突变的杂合携带者。同一密码子处的另一个碱基变化（p.R76S）导致完全显性的ODDD表型。还分析了一例典型的HSS表型病例，但未发现GJA1突变。GJA1纯合亚效突变可导致HSS/ODDD谱系中的一种表型。