{Reference Type}: Case Reports
{Title}: Novel Col12A1 variant expands the clinical picture of congenital myopathies with extracellular matrix defects.
{Author}: Punetha J;Kesari A;Hoffman EP;Gos M;Kamińska A;Kostera-Pruszczyk A;Hausmanowa-Petrusewicz I;Hu Y;Zou Y;Bönnemann CG;JȨdrzejowska M;
{Journal}: Muscle Nerve
{Volume}: 55
{Issue}: 2
{Year}: 02 2017
{Factor}: 3.852
{DOI}: 10.1002/mus.25232
{Abstract}: 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.