<i>COL12A1</i> Gene Variant and a Review of the Literature: A Case Report of Ullrich Congenital Muscular Dystrophy

Abstract

<b><i>Introduction:</i></b> Mutations in collagen type IV-associated genes lead to Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM). <i>COL12A1</i> gene mutations have rarely been reported in patients with UCMD- and BM-like disorders not involving <i>COL6</i> mutations. UCMD-2 results from homozygous mutations in the <i>COL12A1</i> gene on the long arm of chromosome 6. Pathogenic variants in <i>COL12A1</i> result in a rare congenital connective tissue/myopathy overlap syndrome under the heading of myopathic Ehlers-Danlos syndrome. <i>COL12A1</i> dominant pathogenic variants have been rarely reported, and the phenotypic spectrum has not yet been identified. <b><i>Case Presentation:</i></b> We describe a female patient aged 2 years and 10 months exhibiting a milder phenotype who presented due to pronounced joint hyperlaxity, frequent falls, and skin lesions. Genetic analysis revealed a homozygous c.8903C&gt;T (p.Pro2968Leu) missense variant that had previously been described but concerning which there had been no clinical report, in the <i>COL12A1</i> gene. <b><i>Discussion/Conclusion:</i></b> This report is presented in order to raise awareness of rare mutations in the <i>COL12A1</i> gene that affect muscle and connective tissue and to add to the literature in defining the phenotypic spectrum.