Novel mutations identified in patients with a mild phenotype of Ullrich congenital muscular dystrophy through targeted next‐generation sequencing. Issue 4 (26th August 2013)

• Record Type: Journal Article
• Authors: Yuan, Jun‐Hui; Higuchi, Itsuro; Sakiyama, Yusuke; Inamori, Yukie; Matsuura, Eiji; Higuchi, Yujiro; Yoshimura, Akiko; Saigo, Ryuji; Hashiguchi, Akihiro; Higashi, Keiko; Arimura, Kimiyoshi; Takashima, Hiroshi
• Is Part Of: Neurology and clinical neuroscience. Volume 1:Issue 4(2013:Jul.)
• Page Start: 148
• Page End: 153
• Publication Date: 2013-08-26
• Subjects: Neurology -- Periodicals; Neurosciences -- Periodicals; 616.8
• DOI: 10.1111/ncn3.43
• Languages: English
• ISSNs: 2049-4173

Abstract

<abstract abstract-type="main" id="ncn343-abs-0001"> <title>Abstract</title> <sec id="ncn343-sec-0001" sec-type="section"> <title>Aim</title> <p>Ullrich congenital muscular dystrophy, caused by collagen VI deficiency, is heterogeneous in both clinical and pathological phenotype. The aim of the present study was to identify the molecular mechanisms in two sporadic Japanese patients with congenital multiple joint contractures, hyperextension of joints and muscle weakness, but without severe respiratory failure in their 20s.</p> </sec> <sec id="ncn343-sec-0002" sec-type="section"> <title>Methods</title> <p>Collagen VI and several other congenital muscular dystrophy‐related proteins were examined with immunohistochemical staining on biopsies of skeletal muscle. Using a high‐throughput next‐generation sequencing system, we screened the <italic>COL6A1</italic>, <italic> COL6A2</italic> and <italic>COL6A3</italic> genes. A confocal microscopy study was then applied to detect the potential partial deficiency of collagen VI, and to confirm the pathogenicity of the suspected mutations.</p> </sec> <sec id="ncn343-sec-0003" sec-type="section"> <title>Results</title> <p>No diagnostic abnormality was observed by conventional immunohistochemical staining. The mutation screening discovered two novel heterozygous mutations, c.1499G>A (p.G500E) in <italic>COL6A1</italic> and c.801G>T (p.K267N) in <italic>COL6A2</italic>, in patient 1 and 2, respectively. Subsequently, we identified discontinuous expression of collagen VI in the basal lamina and blood vessels by confocal microscopy study.</p> </sec> <sec id="ncn343-sec-0004" sec-type="section"> <title>Conclusion</title> <p>We established a diagnostic procedure for suspected collagen VI‐related disorders, specifically for the patients with a mild phenotype and without diagnostic information in the routine pathological studies. The partially preserved collagen VI in the two patients could be involved in the relatively benign clinical phenotype.</p> </sec> </abstract>