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Muscle Nerve. 2017 Feb;55(2):277-281. doi: 10.1002/mus.25232. Epub 2016 Nov 30.

Novel Col12A1 variant expands the clinical picture of congenital myopathies with extracellular matrix defects.

Author information

1
Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
2
Department of Integrative Systems Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
3
Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
4
Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
5
Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
6
National Institute of Neurological Disorders and Stroke/NIH, Porter Neuroscience Research Center, Bethesda, Maryland, USA.
7
Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.

Abstract

INTRODUCTION:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Bethlem myopathy; Ullrich congenital muscular dystrophy; collagen VI; collagen XII; congenital myopathy; floppy infant; hypotonia; targeted sequencing

PMID:
27348394
PMCID:
PMC5236000
DOI:
10.1002/mus.25232
[Indexed for MEDLINE]
Free PMC Article

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