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Letter to the Editor| Volume 88, ISSUE 1, P141-143, October 01, 2017

Clinical and molecular characterization of a 13-year-old Indian boy with cutis laxa type 2B: Identification of two novel PYCR1 mutations by amplicon-based semiconductor exome sequencing

Published:April 29, 2017DOI:https://doi.org/10.1016/j.jdermsci.2017.04.010
Clinical and molecular characterization of a 13-year-old Indian boy with cutis laxa type 2B: Identification of two novel PYCR1 mutations by amplicon-based semiconductor exome sequencing
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      Autosomal recessive cutis laxa type 2B (ARCL2B, MIM 612940), a.k.a. PYCR1-related ARCL, is a rare disorder characterized by progeroid appearance, generalized skin wrinkling, joint laxity, a characteristic triangular face, hypotonia, and variable central nervous system involvement [
      • Reversade B.
      • Escande-Beillard N.
      • Dimopoulou A.
      • Fischer B.
      • Chng S.C.
      • Li Y.
      • et al.
      Mutations in PYCR1 cause cutis laxa with progeroid features.
      Nat. Genet. 2009; 41: 1016-1021
      ,
      • Dimopoulou A.
      • Fischer B.
      • Gardeitchik T.
      • Schröter P.
      • Kayserili H.
      • Schlack C.
      • et al.
      Genotype-phenotype spectrum of PYCR1-related autosomal recessive cutis laxa.
      Mol. Genet. Metab. 2013; 110: 352-361
      ]. The disease spectrum is wide-ranging and, at the milder end, the phenotype of ARCL2B patients resembles that observed in geroderma osteodysplasticum (GO, MIM 231070, GORAB). GO is characterized by lax skin and wrinkles at dorsa of hands and feet, spontaneous bone fractures due to osteoporosis, jaw hypoplasia and, usually, normal intellectual development [
      • Hennies H.C.
      • Kornak U.
      • Zhang H.
      • Egerer J.
      • Zhang X.
      • Seifert W.
      • et al.
      Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin.
      Nat. Genet. 2008; 40: 1410-1412
      ]. Contrariwise, the more severe affected PYCR1-related ARCL individuals may show pronounced intellectual disability (ID), together with childhood cataract and dystonic movements, consequently, some of these patients are diagnosed as having de Barsy syndrome, also referred to as ARCL type 3 (ARCL3A, MIM 219150, ALDH18A1; ARCL3B, MIM 614438, PYCR1) [
      • Reversade B.
      • Escande-Beillard N.
      • Dimopoulou A.
      • Fischer B.
      • Chng S.C.
      • Li Y.
      • et al.
      Mutations in PYCR1 cause cutis laxa with progeroid features.
      Nat. Genet. 2009; 41: 1016-1021
      ,
      • Zampatti S.
      • Castori M.
      • Fischer B.
      • Ferrari P.
      • Garavelli L.
      • Dionisi-Vici C.
      • et al.
      De Barsy Syndrome: a genetically heterogeneous autosomal recessive cutis laxa syndrome related to P5CS and PYCR1 dysfunction.
      Am. J. Med. Genet. A. 2012; 158: 927-931
      ]. Wrinkled skin and cutis laxa are also observed in ARCL type 1 (ARCL1A, MIM 219100, EFEMP2; ARCL1B, MIM 614437, FBLN5, and ARCL1C, MIM 613177, LTBP4), and type 2A (ARCL2A, MIM 219200, ATP6V0A2). Because of the broad phenotypic overlap, proper diagnosis is challenging. A lack of diagnosis represents a major burden for CL patients considering that severity and prognosis can vary significantly depending upon the specific subtype [
      • Alazami A.M.
      • Al-Qattan S.M.
      • Faqeih E.
      • Alhashem A.
      • Alshammari M.
      • Alzahrani F.
      • et al.
      Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue.
      Hum. Genet. 2016; 135: 525-540
      ,
      • Vanakker O.
      • Callewaert B.
      • Malfait F.
      • Coucke P.
      The genetics of soft connective tissue disorders.
      Annu. Rev. Genomics Hum. Genet. 2015; 16: 229-255
      ]. Furthermore, in several CL patients the underlying genetic defect is not yet known, and the number of causal genes are still growing, as shown by Alazami and coworkers that reported novel CL candidate genes identified by whole-exome sequencing (WES) [
      • Alazami A.M.
      • Al-Qattan S.M.
      • Faqeih E.
      • Alhashem A.
      • Alshammari M.
      • Alzahrani F.
      • et al.
      Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue.
      Hum. Genet. 2016; 135: 525-540
      ].
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      References

        • Reversade B.
        • Escande-Beillard N.
        • Dimopoulou A.
        • Fischer B.
        • Chng S.C.
        • Li Y.
        • et al.
        Mutations in PYCR1 cause cutis laxa with progeroid features.
        Nat. Genet. 2009; 41: 1016-1021
        View in Article
        • Dimopoulou A.
        • Fischer B.
        • Gardeitchik T.
        • Schröter P.
        • Kayserili H.
        • Schlack C.
        • et al.
        Genotype-phenotype spectrum of PYCR1-related autosomal recessive cutis laxa.
        Mol. Genet. Metab. 2013; 110: 352-361
        View in Article
        • Hennies H.C.
        • Kornak U.
        • Zhang H.
        • Egerer J.
        • Zhang X.
        • Seifert W.
        • et al.
        Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin.
        Nat. Genet. 2008; 40: 1410-1412
        View in Article
        • Zampatti S.
        • Castori M.
        • Fischer B.
        • Ferrari P.
        • Garavelli L.
        • Dionisi-Vici C.
        • et al.
        De Barsy Syndrome: a genetically heterogeneous autosomal recessive cutis laxa syndrome related to P5CS and PYCR1 dysfunction.
        Am. J. Med. Genet. A. 2012; 158: 927-931
        View in Article
        • Alazami A.M.
        • Al-Qattan S.M.
        • Faqeih E.
        • Alhashem A.
        • Alshammari M.
        • Alzahrani F.
        • et al.
        Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue.
        Hum. Genet. 2016; 135: 525-540
        View in Article
        • Vanakker O.
        • Callewaert B.
        • Malfait F.
        • Coucke P.
        The genetics of soft connective tissue disorders.
        Annu. Rev. Genomics Hum. Genet. 2015; 16: 229-255
        View in Article
        • Colombi M.
        • Dordoni C.
        • Chiarelli N.
        • Ritelli M.
        Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type compared to other heritable connective tissue disorders.
        Am. J. Med. Genet. C Semin. Med. Genet. 2015; 169C: 6-22
        View in Article
        • Malfait F.
        • Francomano C.
        • Byers P.
        • Belmont J.
        • Berglund B.
        • Black J.
        • et al.
        The 2017 international classification of the Ehlers-Danlos syndromes.
        Am. J. Med. Genet. C Semin. Med. Genet. 2017; 175: 8-26
        View in Article
        • Ritelli M.
        • Chiarelli N.
        • Quinzani S.
        • Dordoni C.
        • Venturini M.
        • Pezzani L.
        • et al.
        Identification of two novel ATP6V0A2 mutations in an infant with cutis laxa by exome sequencing.
        J. Dermatol. Sci. 2014; 75: 66-68
        View in Article
        • Phang J.M.
        • Pandhare J.
        • Liu Y.
        The metabolism of proline as microenvironmental stress substrate.
        J. Nutr. 2008; 138: 2008S-2015S
        View in Article

      Article Info

      Publication History

      Published online: April 29, 2017
      Received: September 8, 2016

      Identification

      DOI: https://doi.org/10.1016/j.jdermsci.2017.04.010

      Copyright

      © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

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