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Recessive Mutations in AP1B1 Cause Ichthyosis, Deafness, and Photophobia.

ABSTRACT: 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 ? subunit of heterotetrameric adaptor protein 1 (AP-1) complexes, which mediate endomembrane polarization, sorting, and transport. In affected keratinocytes the AP-1 ? subunit is lost, and the ? 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.

SUBMITTER: Boyden LM

PROVIDER: S-EPMC6849088 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Recessive Mutations in AP1B1 Cause Ichthyosis, Deafness, and Photophobia.

Boyden Lynn M LM Atzmony Lihi L Hamilton Claire C Zhou Jing J Lim Young H YH Hu Ronghua R Pappas John J Rabin Rachel R Ekstien Joseph J Hirsch Yoel Y Prendiville Julie J Lifton Richard P RP Ferguson Shawn S Choate Keith A KA

American journal of human genetics 20191017 5

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 β subunit of heterotetrameric adaptor protein 1 (AP-1) complexes, which mediate endomembrane polarization, sorting, and transport. In affected keratinocytes the AP-1 β subunit is lost, and the γ subunit is greatly reduced, demonstrating destabilization of the AP-1 complex. Affected cells and tissue contai ...[more]

PMID: 31630788

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