RESUMO
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.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Colesterol/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/genética , Cabelo/crescimento & desenvolvimento , Hipertricose/congênito , Pré-Escolar , Colesterol/genética , Deleção Cromossômica , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Cabelo/patologia , Humanos , Hipertricose/genética , Hipertricose/patologia , Lactente , Queratinócitos/metabolismo , Queratinócitos/patologia , Mutação , Linhagem , Fenótipo , Splicing de RNA/genética , Deleção de SequênciaRESUMO
We report the case of a girl with hypertrichosis lanuginosa congenita treated with diode laser depilation since the age of 9 months. The treatment was well tolerated, and neither general nor local anesthesia was needed. A reduction of approximately 80% of facial and body hair was noted, which improved her condition significantly.
Assuntos
Remoção de Cabelo/métodos , Hipertricose/congênito , Lasers Semicondutores/uso terapêutico , Feminino , Cabelo , Humanos , Hipertricose/terapia , LactenteRESUMO
Focal acral hyperkeratosis is characterized by the same clinical appearance as acrokeratoelastoidosis, but without abnormalities in the elastic fibers. We present the case of a woman with a 10-year case of dermatosis localized on the palms, soles and dorsum of the metacarpophalangeal joints, consisting of multiple polygonal papules and associated hyperhydrosis, clinically compatible with acrokeratoelastoidosis. Her father had a history of the disease. In addition, the patient presented with palmoplantar pitted keratolysis. The histopathological study ruled out elastorrhexis, and the pitted keratolysis was corroborated by the clinical appearance and the presence of coccoid elements in the stratum corneum, evident with a PAS stain. In our opinion, the focal acral hyperkeratosis is not a separate entity from the acrokeratoelastoidosis.