Advertisement

First Japanese case of congenital generalized hypertrichosis with a copy number variation on chromosome 17q24

      Hypertrichosis is defined as excessive hair growth compared with individuals of the same age, race and sex [
      • Wendelin D.S.
      • Pope D.N.
      • Mallory S.B.
      Hypertrichosis.
      ]. Congenital generalized hypertrichosis (CGH) is a rare syndrome characterized by universal hair overgrowth which is not caused by androgen stimulation [
      • Wendelin D.S.
      • Pope D.N.
      • Mallory S.B.
      Hypertrichosis.
      ,
      • Garcia-Cruz D.
      • Figuera L.E.
      • Cantu J.M.
      Inherited hypertrichoses.
      ]. In addition to hypertrichosis, patients with CGH can have other associated abnormalities, such as cardiomyopathy and gingival hyperplasia [
      • Wendelin D.S.
      • Pope D.N.
      • Mallory S.B.
      Hypertrichosis.
      ,
      • Garcia-Cruz D.
      • Figuera L.E.
      • Cantu J.M.
      Inherited hypertrichoses.
      ]. CGH can show X-linked recessive (OMIM 307150), autosomal dominant or autosomal recessive (OMIM 135400) inheritance trait, and recent advances in molecular genetics have gradually disclosed the pathogenesis of CGH [
      • Fantauzzo K.A.
      • Tadin-Strapps M.
      • You Y.
      • Mentzer S.E.
      • Baumeister F.A.
      • Cianfarani S.
      • et al.
      A position effect on TRPS1 is associated with Ambras syndrome in humans and the Koala phenotype in mice.
      ,
      • Sun M.
      • Li N.
      • Dong W.
      • Chen Z.
      • Liu Q.
      • Xu Y.
      • et al.
      Copy-number mutations on chromosome 17q24.2-q24.3 in congenital generalized hypertrichosis terminalis with or without gingival hyperplasia.
      ,
      • DeStefano G.M.
      • Fantauzzo K.A.
      • Petukhova L.
      • Kurban M.
      • Tadin-Strapps M.
      • Levy B.
      • et al.
      Position effect on FGF13 associated with X-linked congenital generalized hypertrichosis.
      ,
      • DeStefano G.M.
      • Kurban M.
      • Anyane-Yeboa K.
      • Dall’Armi C.
      • Di Paolo G.
      • Feenstra H.
      • et al.
      Mutations in the cholesterol transporter gene ABCA5 are associated with excessive hair overgrowth.
      ]. Of these findings, it has been reported that autosomal dominant form of CGH with or without gingival hyperplasia is caused by copy number variations (CNVs) on chromosome (Ch) 17q24.2-q24.3 [
      • Sun M.
      • Li N.
      • Dong W.
      • Chen Z.
      • Liu Q.
      • Xu Y.
      • et al.
      Copy-number mutations on chromosome 17q24.2-q24.3 in congenital generalized hypertrichosis terminalis with or without gingival hyperplasia.
      ]. Interestingly, SOX9 gene, which is known to play a role in maintenance of hair follicle (HF) stem cells [
      • Nowak J.A.
      • Polak L.
      • Pasolli H.A.
      • Fuchs E.
      Hair follicle stem cells are specified and function in early skin morphogenesis.
      ,
      • Kadaja M.
      • Keyes B.E.
      • Lin M.
      • Pasolli H.A.
      • Genander M.
      • Polak L.
      • et al.
      SOX9: a stem cell transcriptional regulator of secreted niche signaling factors.
      ], is located close to the region of the CNVs, and it has been demonstrated that a CNV on Ch17q24.2-q24.3 resulted in reduced expression of the SOX9-mRNA, most likely due to a position effect [
      • DeStefano G.M.
      • Kurban M.
      • Anyane-Yeboa K.
      • Dall’Armi C.
      • Di Paolo G.
      • Feenstra H.
      • et al.
      Mutations in the cholesterol transporter gene ABCA5 are associated with excessive hair overgrowth.
      ]. Furthermore, autosomal recessive form of CGH has been shown to be caused by a loss-of-function mutation in ABCA5 gene encoding a member of the ABC transporter [
      • DeStefano G.M.
      • Kurban M.
      • Anyane-Yeboa K.
      • Dall’Armi C.
      • Di Paolo G.
      • Feenstra H.
      • et al.
      Mutations in the cholesterol transporter gene ABCA5 are associated with excessive hair overgrowth.
      ]. Importantly, the ABCA5 gene resides on Ch17q24.3, where the CNVs occurred in patients with autosomal dominant CGH [
      • Sun M.
      • Li N.
      • Dong W.
      • Chen Z.
      • Liu Q.
      • Xu Y.
      • et al.
      Copy-number mutations on chromosome 17q24.2-q24.3 in congenital generalized hypertrichosis terminalis with or without gingival hyperplasia.
      ]. Besides these findings, however, the molecular basis of CGH in Japanese population had remained totally unknown. In this study, we analyzed a Japanese female patient with CGH and successfully identified a CNV on Ch17q24. We further investigated how the CNV affected expression of SOX9 and ABCA5 proteins in the patient’s HFs. The detailed Materials and Methods are shown elsewhere (Supplementary information online).
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Dermatological Science
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Wendelin D.S.
        • Pope D.N.
        • Mallory S.B.
        Hypertrichosis.
        J. Am. Acad. Dermatol. 2003; 48: 161-179
        • Garcia-Cruz D.
        • Figuera L.E.
        • Cantu J.M.
        Inherited hypertrichoses.
        Clin. Genet. 2002; 61: 321-329
        • Fantauzzo K.A.
        • Tadin-Strapps M.
        • You Y.
        • Mentzer S.E.
        • Baumeister F.A.
        • Cianfarani S.
        • et al.
        A position effect on TRPS1 is associated with Ambras syndrome in humans and the Koala phenotype in mice.
        Hum. Mol. Genet. 2008; 17: 3539-3551
        • Sun M.
        • Li N.
        • Dong W.
        • Chen Z.
        • Liu Q.
        • Xu Y.
        • et al.
        Copy-number mutations on chromosome 17q24.2-q24.3 in congenital generalized hypertrichosis terminalis with or without gingival hyperplasia.
        Am. J. Hum. Genet. 2009; 84: 807-813
        • DeStefano G.M.
        • Fantauzzo K.A.
        • Petukhova L.
        • Kurban M.
        • Tadin-Strapps M.
        • Levy B.
        • et al.
        Position effect on FGF13 associated with X-linked congenital generalized hypertrichosis.
        Proc. Natl. Acad. Sci. U. S. A. 2013; 110: 7790-7795
        • DeStefano G.M.
        • Kurban M.
        • Anyane-Yeboa K.
        • Dall’Armi C.
        • Di Paolo G.
        • Feenstra H.
        • et al.
        Mutations in the cholesterol transporter gene ABCA5 are associated with excessive hair overgrowth.
        PLoS Genet. 2014; 10: e1004333
        • Nowak J.A.
        • Polak L.
        • Pasolli H.A.
        • Fuchs E.
        Hair follicle stem cells are specified and function in early skin morphogenesis.
        Cell Stem Cell. 2008; 3: 33-43
        • Kadaja M.
        • Keyes B.E.
        • Lin M.
        • Pasolli H.A.
        • Genander M.
        • Polak L.
        • et al.
        SOX9: a stem cell transcriptional regulator of secreted niche signaling factors.
        Genes Dev. 2014; 28: 328-341
        • Kubo Y.
        • Sekiya S.
        • Ohigashi M.
        • Takenaka C.
        • Tamura K.
        • Nada S.
        • et al.
        ABCA5 resides in lysosomes, and ABCA5 knockout mice develop lysosomal disease-like symptoms.
        Mol. Cell. Biol. 2005; 25: 4138-4149
        • Takenaka S.
        • Itoh T.
        • Fujiwara R.
        Expression pattern of human ATP-binding cassette transporters in skin.
        Pharmacol. Res. Perspect. 2013; 1: e00005