Mutations in the Cholesterol Transporter Gene Are Associated with Excessive Hair Overgrowth

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Inherited hypertrichoses represent a group of hair overgrowth syndromes that are extremely rare in humans and have remained an area of great interest to evolutionary geneticists since they are considered to be recurrences of an ancestral phenotype. These syndromes often present with additional congenital abnormalities including bone, heart and dental defects; thus, it is crucial to identify the mechanisms and genes underlying the pathology. Copy number variants (CNVs) have previously been reported in several cases of congenital generalized hypertrichosis terminalis (CGHT) with a minimal overlapping region of 555 kb encompassing four genes. However, no point mutations in these or any other single genes have been described to underlie the CGHT phenotype. In this study, we report the first loss-of-function mutation in an ABC transporter, ABCA5 and identified an additional copy number variant in a separate case that lies within the minimal common region. We found high levels of ABCA5 expression in both epithelial and mesenchymal compartments of human and mouse hair follicles, and in CGHT patients, this expression is significantly reduced or completely lost. ABCA5 is a lysosomal protein, and its loss-of-function compromises the integrity of lysosomes and leads to an intra-endolysosomal accumulation of cholesterol. Importantly, our findings support a novel role for ABCA5 in regulating hair growth.

Vyšlo v časopise: Mutations in the Cholesterol Transporter Gene Are Associated with Excessive Hair Overgrowth. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004333
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004333

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