6533b825fe1ef96bd12828c3
RESEARCH PRODUCT
Mutations in FAM111B Cause Hereditary Fibrosing Poikiloderma with Tendon Contracture, Myopathy, and Pulmonary Fibrosis
Pierre LindenbaumRomain K. GherardiNathalie BodakSébastien BarbarotDarren T. HounietValérie Cormier-daireDominique Figarella-brangerLaurence FaivreRichard RedonChristian L. LaboisseCédric Le CaignecNonhlanhla P. KhumaloEmmanuelle Salort-campanaStéphane BézieauAntoine HamelArmelle MagotChantal Bou-hannaJean-marie MussiniArnold MunnichMauro Santibanez-korefChristel ThauvinKomala PillaySandra MercierElise GlenAlbert DavidGasnat ShaboodienThahira RahmanBongani M. MayosiSébastien KüryBernard KeavneyBernard Keavneysubject
AdultMalePathologymedicine.medical_specialtyContractureAdolescentPulmonary FibrosisPoikilodermaCell Cycle Proteinsmedicine.disease_causeTendonssymbols.namesakeYoung AdultMuscular DiseasesReportPulmonary fibrosismedicineGeneticsMissense mutationHumansGenetics(clinical)MyopathyChildRothmund–Thomson syndromeGenetics (clinical)Sanger sequencingMutationbusiness.industryInfant NewbornRothmund-Thomson SyndromeInfantmedicine.diseasePedigreePhenotypeChild PreschoolMutationsymbolsFemalemedicine.symptomContracturebusinessdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-12-01 |