title: Novel Col12A1 variant expands the clinical picture of congenital myopathies with extracellular matrix defects.
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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.|Department of Integrative Systems Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Punetha
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Akanchha
authors.initials: A
authors.lastname: Kesari
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.|Department of Integrative Systems Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Gos
authors.affiliation: Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kamińska
authors.affiliation: Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kostera-Pruszczyk
authors.affiliation: Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Hausmanowa-Petrusewicz
authors.affiliation: National Institute of Neurological Disorders and Stroke/NIH, Porter Neuroscience Research Center, Bethesda, Maryland, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: National Institute of Neurological Disorders and Stroke/NIH, Porter Neuroscience Research Center, Bethesda, Maryland, USA.
authors.forename: Yaqun
authors.initials: Y
authors.lastname: Zou
authors.affiliation: National Institute of Neurological Disorders and Stroke/NIH, Porter Neuroscience Research Center, Bethesda, Maryland, USA.
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Bönnemann
authors.affiliation: Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.|Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: JȨdrzejowska
mesh_terms: D002648:Child; D024082:Collagen Type XII / Q000235:genetics*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C547160:COL12A1 protein, human; D024082:Collagen Type XII
keywords: Bethlem myopathy; Ullrich congenital muscular dystrophy; collagen VI; collagen XII; congenital myopathy; floppy infant; hypotonia; targeted sequencing