Mutations in the Cholesterol Transporter Gene ABCA5 Are Associated with Excessive Hair Overgrowth

Gina M. DeStefano, Mazen Kurban, Kwame Anyane-Yeboa, Claudia Dall'Armi, Gilbert Di Paolo, Heather Feenstra, Nanette Silverberg, Luis Rohena, Larissa D. López-Cepeda, Vaidehi Jobanputra, Katherine A. Fantauzzo, Maija Kiuru, Marija Tadin-Strapps, Antonio Sobrino, Anna Vitebsky, Dorothy Warburton, Brynn Levy, Julio C. Salas-Alanis, Angela M. Christiano

Resultado de la investigaciónrevisión exhaustiva

27 Citas (Scopus)

Resumen

Inherited hypertrichoses are rare syndromes characterized by excessive hair growth that does not result from androgen stimulation, and are often associated with additional congenital abnormalities. In this study, we investigated the genetic defect in a case of autosomal recessive congenital generalized hypertrichosis terminalis (CGHT) (OMIM135400) using whole-exome sequencing. We identified a single base pair substitution in the 5′ donor splice site of intron 32 in the ABC lipid transporter gene ABCA5 that leads to aberrant splicing of the transcript and a decrease in protein levels throughout patient hair follicles. The homozygous recessive disruption of ABCA5 leads to reduced lysosome function, which results in an accumulation of autophagosomes, autophagosomal cargos as well as increased endolysosomal cholesterol in CGHT keratinocytes. In an unrelated sporadic case of CGHT, we identified a 1.3 Mb cryptic deletion of chr17q24.2-q24.3 encompassing ABCA5 and found that ABCA5 levels are dramatically reduced throughout patient hair follicles. Collectively, our findings support ABCA5 as a gene underlying the CGHT phenotype and suggest a novel, previously unrecognized role for this gene in regulating hair growth.

Idioma originalEnglish
Número de artículoe1004333
PublicaciónPLoS Genetics
Volumen10
N.º5
DOI
EstadoPublished - may 2014

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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