title: Mutations in FAM111B cause hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis.
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.
authors.affiliation: 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.
authors.forename: Sandra
authors.initials: S
authors.lastname: Mercier
authors.forename: Sébastien
authors.initials: S
authors.lastname: Küry
authors.forename: Gasnat
authors.initials: G
authors.lastname: Shaboodien
authors.forename: Darren T
authors.initials: DT
authors.lastname: Houniet
authors.forename: Nonhlanhla P
authors.initials: NP
authors.lastname: Khumalo
authors.forename: Chantal
authors.initials: C
authors.lastname: Bou-Hanna
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bodak
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: Romain K
authors.initials: RK
authors.lastname: Gherardi
authors.forename: Elise
authors.initials: E
authors.lastname: Glen
authors.forename: Antoine
authors.initials: A
authors.lastname: Hamel
authors.forename: Christian
authors.initials: C
authors.lastname: Laboisse
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Caignec
authors.forename: Pierre
authors.initials: P
authors.lastname: Lindenbaum
authors.forename: Armelle
authors.initials: A
authors.lastname: Magot
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Mussini
authors.forename: Komala
authors.initials: K
authors.lastname: Pillay
authors.forename: Thahira
authors.initials: T
authors.lastname: Rahman
authors.forename: Richard
authors.initials: R
authors.lastname: Redon
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Salort-Campana
authors.forename: Mauro
authors.initials: M
authors.lastname: Santibanez-Koref
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin
authors.forename: Sébastien
authors.initials: S
authors.lastname: Barbarot
authors.forename: Bernard
authors.initials: B
authors.lastname: Keavney
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bézieau
authors.forename: Bongani M
authors.initials: BM
authors.lastname: Mayosi
mesh_terms: D000293:Adolescent; D000328:Adult; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003286:Contracture / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009135:Muscular Diseases / Q000150:complications*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011658:Pulmonary Fibrosis / Q000150:complications*; D011038:Rothmund-Thomson Syndrome / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D013710:Tendons / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; C586301:FAM111B protein, human