Mutations in FAM111B Cause Hereditary Fibrosing Poikiloderma with Tendon Contracture, Myopathy, and Pulmonary Fibrosis

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 thr…

A phase I/II clinical trial of autologous myoblast transplantation in facioscapulohumeral muscular dystrophy

International audience; Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is one of the most frequent adult myopathies (1/20.000), with selective involvement of specific groups of muscles : facial, scapular fixator, anterior foreleg muscles, abdominal and humeral muscles. Vastus lateralis (VL) is usually spared clinically until late stages of the disease, and myoblasts grown from VL have similar behaviour in vivo and in vitro than myoblasts from control patients-> Proposal:Transplantation of autologous myoblast from spared muscle (VL) into an affected muscle as the Tibialis anterior (TA) muscle could locally improve the muscle’s regenerative capacities. Results and discussion: Cell prod…

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations

Background Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. Methods Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. Results Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypoh…

Systematic retrospective study of 64 patients with anti-Mi2 dermatomyositis: A classic skin rash with a necrotizing myositis and high risk of malignancy