%0 Journal Article
%T Case report of intrafamilial variability in autosomal recessive centronuclear myopathy associated to a novel BIN1 stop mutation
%A Johann B£¿hm
%A Ulu£¿ Yi£¿
%A Rag£¿p Orta£¿
%A Handan £¿akmak£¿£¿
%A Semra Kurul
%A Eray Dirik
%A Jocelyn Laporte
%J Orphanet Journal of Rare Diseases
%D 2010
%I BioMed Central
%R 10.1186/1750-1172-5-35
%X Centronuclear myopathies (CNM) are a group of congenital disorders characterized by hypotonia and skeletal muscle biopsies typically showing small rounded fibers with central nuclei [1-4]. Abnormal nuclear positioning is seen in several myopathies, but clinical, genetic and pathological factors clearly distinguish these myopathies from CNM. Three CNM classes have been described: the severe neonatal X-linked form, also called myotubular myopathy (XLCNM, OMIM 310400), the autosomal recessive form with childhood onset (ARCNM, OMIM 255200), and the autosomal dominant form with adult onset (ADCNM, OMIM 160150). Myotubularin (MTM1) is mutated in XLCNM [5] and belongs to a large family of ubiquitously expressed phosphoinositide phosphatases implicated in intracellular vesicle trafficking [6-8]. The large GTPase dynamin 2 (DNM2), mutated in ADCNM, is a mechanochemical enzyme and a key factor in membrane trafficking and endocytosis [9-11]. Amphiphysin 2 (BIN1) is mutated in ARCNM and possesses an N-terminal BAR domain able to sense and bend membranes and a SH3 domain mediating protein-protein interactions [12,13]. A muscle-specific isoform is implicated in T-tubule biogenesis and contains a polybasic residue sequence binding to phosphoinositides [14]. Only 4 unrelated individuals with BIN1 mutations have been molecularly and clinically characterized to date [12,15] and this report is the first description of intrafamilal variability in two patients from a consanguineous family. Clinical analysis of respiratory and cardiac involvement diagnosed for the more severely affected male patient expand the phenotypic spectrum in autosomal recessive centronuclear myopathy. It is furthermore the first time that patients with a BIN1 mutation are analyzed by whole-body MRI and the results contrast previous findings on DNM2-related CNM.Patient 1 is a 13 year old girl belonging to a consanguineous family from Turkey without ancestral history of neuromuscular disorders (Figure 1A-B). There
%U http://www.ojrd.com/content/5/1/35