%0 Case Reports
%T Novel Col12A1 variant expands the clinical picture of congenital myopathies with extracellular matrix defects.
%A Punetha J
%A Kesari A
%A Hoffman EP
%A Gos M
%A Kamińska A
%A Kostera-Pruszczyk A
%A Hausmanowa-Petrusewicz I
%A Hu Y
%A Zou Y
%A Bönnemann CG
%A JȨdrzejowska M
%J Muscle Nerve
%V 55
%N 2
%D 02 2017
%M 27348394
%F 3.852
%R 10.1002/mus.25232
%X Mutations in the COL12A1 (collagen, type XII, alpha 1) gene have been described in a milder Bethlem-like myopathy in 6 patients from 3 families (dominant missense), and in a severe congenital form with failure to attain ambulation in 2 patients in a single pedigree (recessive loss-of-function).<BR>We describe an 8-year-old girl of Polish origin who presented with profound hypotonia and joint hyperlaxity at birth after a pregnancy complicated by oligohydramnios and intrauterine growth retardation.<BR>We identified a novel, potentially pathogenic heterozygous missense COL12A1 c.8329G>C (p.Gly2777Arg) variant using a targeted sequencing panel. Patient fibroblast studies confirmed intracellular retention of the COL12A1 protein, consistent with a dominant-negative mutation.<BR>As our patient showed a more intermediate phenotype, this case expands the phenotypic spectrum for COL12A1 disorders. So far, COL12A1 disorders seem to cover much of the severity range of an Ehlers-Danlos/Bethlem-like myopathy overlap syndrome associated with both connective tissue abnormalities and muscle weakness. Muscle Nerve 55: 277-281, 2017.