2. Academic Validation
  3. Mutations in FAM111B cause hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis

Mutations in FAM111B cause hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis

  • Am J Hum Genet. 2013 Dec 5;93(6):1100-7. doi: 10.1016/j.ajhg.2013.10.013.
Sandra Mercier 1,  Sébastien Küry,  Gasnat Shaboodien,  Darren T Houniet,  Nonhlanhla P Khumalo,  Chantal Bou-Hanna,  Nathalie Bodak,  Valérie Cormier-Daire,  Albert David,  Laurence Faivre,  Dominique Figarella-Branger,  Romain K Gherardi,  Elise Glen,  Antoine Hamel,  Christian Laboisse,  Cédric Le Caignec,  Pierre Lindenbaum,  Armelle Magot,  Arnold Munnich,  Jean-Marie Mussini,  Komala Pillay,  Thahira Rahman,  Richard Redon,  Emmanuelle Salort-Campana,  Mauro Santibanez-Koref,  Christel Thauvin,  Sébastien Barbarot,  Bernard Keavney,  Stéphane Bézieau,  Bongani M Mayosi
Affiliations

Affiliation

  • 1 Unité de Génétique Clinique, Service de Génétique Médicale, Centre de Référence Anomalies de Développement et Syndromes Malformatifs de l'Interrégion Grand-Ouest, Centre Hospitalier Universitaire Nantes, 9 Quai Moncousu, 44093 Nantes Cedex 1, France; Institut National de la Santé et de la Recherche Médicale UMR 1089, Atlantic Gene Therapy Institute, University of Nantes, 44007 Nantes, France.
PMID: 24268661 DOI: 10.1016/j.ajhg.2013.10.013
Abstract

Congenital poikiloderma is characterized by a combination of mottled pigmentation, telangiectasia, and epidermal atrophy in the first few months of life. We have previously described a South African European-descent family affected by a rare autosomal-dominant form of hereditary fibrosing poikiloderma accompanied by tendon contracture, myopathy, and pulmonary fibrosis. Here, we report the identification of causative mutations in FAM111B by whole-exome Sequencing. In total, three FAM111B missense mutations were identified in five kindreds of different ethnic backgrounds. The mutation segregated with the disease in one large pedigree, and mutations were de novo in two Other pedigrees. All three mutations were absent from public databases and were not observed on Sanger Sequencing of 388 ethnically matched control subjects. The three single-nucleotide mutations code for amino acid changes that are clustered within a putative trypsin-like cysteine/serine peptidase domain of FAM111B. These findings provide evidence of the involvement of FAM111B in congenital poikiloderma and multisystem fibrosis.

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