期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 67, 期 6, 页码 1555-1562出版社
CELL PRESS
DOI: 10.1086/316914
关键词
-
资金
- NCRR NIH HHS [M01 RR01271, M01 RR001271] Funding Source: Medline
- NIDCR NIH HHS [R01 DE011311, DE11311] Funding Source: Medline
Hypohidrotic ectodermal dysplasia (HED), a congenital disorder of teeth, hair, and eccrine sweat glands, is usually inherited as an X-linked recessive trait, although rarer autosomal dominant and recessive forms exist. We have studied males from four families with HED and immunodeficiency (HED-ID), in which the disorder segregates as an X-linked recessive trait. Affected males manifest dysgammaglobulinemia and, despite therapy, have significant morbidity and mortality from recurrent infections. Recently, mutations in IKK-gamma (NEMO) have been shown to cause familial incontinentia pigmenti (LP). Unlike HED-ID, IP affects females and, with few exceptions, causes male prenatal lethality. Wt-gamma is required for the activation of the transcription factor known as nuclear factor kappa B and plays an important role in T and B cell function. We hypothesize that milder mutations at this locus may cause HED-ID. In all four families, sequence analysis reveals exon 10 mutations affecting the carboxy-terminal end of the IKK-gamma protein, a domain believed to connect the IKK signalsome complex to upstream activators. The findings define a new X-linked recessive immunodeficiency syndrome, distinct from other types of HED and immunodeficiency syndromes. The data provide further evidence that the development of ectodermal appendages is mediated through a tumor necrosis factor/tumor necrosis factor receptor-like signaling pathway, with the IKK signalsome complex playing a significant role.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据