当前位置： SCI文献检索 > Orphanet Journal of Rare Diseases期刊下所有文献 > Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations.

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

Abstract：

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 hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS:HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder.

journal_name

Orphanet J Rare Dis

journal_title

Orphanet journal of rare diseases

authors

Mercier S,Küry S,Salort-Campana E,Magot A,Agbim U,Besnard T,Bodak N,Bou-Hanna C,Bréhéret F,Brunelle P,Caillon F,Chabrol B,Cormier-Daire V,David A,Eymard B,Faivre L,Figarella-Branger D,Fleurence E,Ganapathi M,Gherard

doi

10.1186/s13023-015-0352-4

subject

Has Abstract

pub_date

2015-10-15 00:00:00

pages

135

issn

1750-1172

pii

10.1186/s13023-015-0352-4

journal_volume

pub_type

杂志文章

在线工具

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