Additional file 1: of Molecular pathomechanisms and cell-type-specific disease phenotypes of MELAS caused by mutant mitochondrial tRNATrp

Supplementary Figures and Tables. (DOC 4252 kb) Figure S1. Comparison of mitochondrial tRNATrp stability between wild-type and m.5541C > T mutant (related to Fig. 1). Figure S2. Protein modeling and amino acid sequences of each mtDNA-encoded CIV subunit (related to Fig. 2). Figure S3. Generation of disease-relevant iPSCs carrying all mutant mitochondrial tRNATrp (related to Fig. 3). Figure S4. Mutant mitochondrial tRNATrp strongly impairs neuronal maturation (related to Fig. 4). Table S1. mtDNA sequence variants in this patient. Table S2. Primer list. Table S3. TaqMan probe list

Association between <i>C8orf13–BLK</i> rs13277113 and polymyositis/dermatomyositis.

<p>OR: Odds ratio, CI: confidence interval, PM: polymyositis, DM: dermatomyositis, N.S.: not significant.</p

Summary of clinical and pathological findings of BMD patients with rimmed vacuoles.

<p>BB = biceps brachii; QF = quadriceps femoris; RF = rectus femoris; BF = biceps femoris; *per 1,000 fibers</p

Pathological Characteristics of BMD patients. A:

<p>On mGT staining, RVs are seen in the periphery of myofibers (<b>arrow</b>). <b>B:</b> On H&E staining, there is marked variation in fiber size with scattered small atrophic fibers. <b>C:</b> High acid phosphatase activity is seen in the areas of RVs. <b>D:</b> On ATPase staining pre-incubated at pH 4.6, RVs are seen in both type 1 and type 2 fibers. <b>Asterisks</b> indicate myofibers with RVs. Scale bar: 25 µm.</p

Areas of RVs in BMD myofibers show typical electron microscopic characteristics of autophagic vacuoles. A:

<p>Accumulation of autophagic vacuoles (<b>arrowheads</b>), various cellular debris, and multilamellar bodies (<b>arrow</b>) are seen in myofibers of some BMD patients. Note the intact arrangement of myofibrils (<b>MF</b>) surrounding autophagic area. B: In areas with or without autophagy, lipofuscin deposit (<b>L</b>) is seen. Scale bars: 1 µm.</p

Summary of clinical and pathological findings of BMD patients without RVs (<i>DMD</i> deletion exons 45–47 and 45–48).

<p>QF = quadriceps femoris; BB = biceps brachii; GC = gastrocnemius; TA = tibialis anterior; *per 1,000 fibers</p

Additional file 1: Table S1. of Comprehensive analysis for genetic diagnosis of Dystrophinopathies in Japan

Clinical and dystrophin immunostaining in the patients with a small mutation. Table S2. Patients with nonsense mutation and faint&patchy dystrophin staining. (PDF 286 kb

Comprehensive target capture/next-generation sequencing as a second-tier diagnostic approach for congenital muscular dystrophy in Taiwan

<div><p>Purpose</p><p>Congenital muscular dystrophy (CMD) is a heterogeneous disease entity. The detailed clinical manifestation and causative gene for each subgroup of CMD are quite variable. This study aims to analyze the phenotypes and genotypes of Taiwanese patients with CMD as the epidemiology of CMD varies among populations and has been scantly described in Asia.</p><p>Methods</p><p>A total of 48 patients suspected to have CMD were screened and categorized by histochemistry and immunohistochemistry studies. Different genetic analyses, including next-generation sequencing (NGS), were selected, based on the clinical and pathological findings.</p><p>Results</p><p>We identified 17 patients with sarcolemma-specific collagen VI deficiency (SSCD), 6 patients with merosin deficiency, two with reduced alpha-dystroglycan staining, and two with striking lymphocyte infiltration in addition to dystrophic change on muscle pathology. Fourteen in 15 patients with SSCD, were shown to have <i>COL6A</i>1, <i>COL6A2</i> or <i>COL6A3</i> mutations by NGS analysis; all showed marked distal hyperlaxity and normal intelligence but the overall severity was less than in previously reported patients from other populations. All six patients with merosin deficiency had mutations in <i>LAMA2</i>. They showed relatively uniform phenotype that were compatible with previous studies, except for higher proportion of mental retardation with epilepsy. With reduced alpha-dystroglycan staining, one patient was found to carry mutations in <i>POMT1</i> while another patient carried mutations in <i>TRAPPC11</i>. <i>LMNA</i> mutations were found in the two patients with inflammatory change on muscle pathology. They were clinically characterized by neck flexion limitation and early joint contracture, but no cardiac problem had developed yet.</p><p>Conclusion</p><p>Muscle pathology remains helpful in guiding further molecular analyses by direct sequencing of certain genes or by target capture/NGS as a second-tier diagnostic tool, and is crucial for establishing the genotype-phenotype correlation. We also determined the frequencies of the different types of CMD in our cohort which is important for the development of a specific care system for each disease.</p></div

Pedigree and sequencing results of the patients with L-CMD.

<p>Pedigree and sequencing results of the patients with L-CMD.</p

Summary of the patients with UCMD.

<p>Summary of the patients with UCMD.</p