Recessive Mutations in AP1B1 Cause Ichthyosis, Deafness, and Photophobia
Recessive Mutations in AP1B1 Cause Ichthyosis, Deafness, and Photophobia
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DOI：
10.1016/j.ajhg.2019.09.021
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发表时间：
2019-11-07
影响因子：
9.8
通讯作者：
Choate, Keith A.
中科院分区：
文献类型：
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作者：
Boyden, Lynn M.;Atzmony, Lihi;Choate, Keith A.
我们描述了患有鱼鳞病、发育迟缓、血小板减少、畏光和进行性听力损失的无关个体。每个都在 AP1B1 中存在双等位基因突变，AP1B1 是编码异四聚体衔接蛋白 1 (AP-1) 复合物 β 亚基的基因，介导内膜极化、分选和运输。在受影响的角质形成细胞中，AP-1 β 亚基丢失，而 γ 亚基大大减少，表明 AP-1 复合物不稳定。受影响的细胞和组织含有大量异常囊泡，并表现出过度增殖、异常表皮分化和细胞间连接蛋白紊乱。用野生型 AP1B1 转导受影响的细胞可挽救囊泡表型，最终确定 AP1B1 功能的丧失导致了这种疾病。
We describe unrelated individuals with ichthyosis, failure to thrive, thrombocytopenia, photophobia, and progressive hearing loss. Each have bi-allelic mutations in AP1B1, the gene encoding the beta subunit of heterotetrameric adaptor protein 1 (AP-1) complexes, which mediate endomembrane polarization, sorting, and transport. In affected keratinocytes the AP-1 beta subunit is lost, and the gamma subunit is greatly reduced, demonstrating destabilization of the AP-1 complex. Affected cells and tissue contain an abundance of abnormal vesicles and show hyperproliferation, abnormal epidermal differentiation, and derangement of intercellular junction proteins. Transduction of affected cells with wild-type AP1B1 rescues the vesicular phenotype, conclusively establishing that loss of AP1B1 function causes this disorder.