Extension of the DNAJB2a isoform in a dominant neuromyopathy family.

Recessive mutations in the DNAJB2 gene, encoding the J-domain co-chaperones DNAJB2a and DNAJB2b, have previously been reported as the genetic cause of progressive peripheral neuropathies, rarely involving pyramidal signs, parkinsonism and myopathy. We describe here a family with the first dominantly acting DNAJB2 mutation resulting in a late-onset neuromyopathy phenotype. The c.

Dominant Distal Myopathy 3 (MPD3) Caused by a Deletion in the Gene.

Background And Objectives: To determine the genetic cause of the disease in the previously reported family with adult-onset autosomal dominant distal myopathy (myopathy, distal, 3; MPD3).

Methods: Continued clinical evaluation including muscle MRI and muscle pathology. A linkage analysis with single nucleotide polymorphism arrays and genome sequencing were used to identify the genetic defect, which was verified by Sanger sequencing.

Missense mutations in small muscle protein X-linked (SMPX) cause distal myopathy with protein inclusions.

Using deep phenotyping and high-throughput sequencing, we have identified a novel type of distal myopathy caused by mutations in the Small muscle protein X-linked (SMPX) gene. Four different missense mutations were identified in ten patients from nine families in five different countries, suggesting that this disease could be prevalent in other populations as well. Haplotype analysis of patients with similar ancestry revealed two different founder mutations in Southern Europe and France, indicating that the prevalence in these populations may be higher.

Genotype-phenotype correlations in recessive titinopathies.

Purpose: High throughput sequencing analysis has facilitated the rapid analysis of the entire titin (TTN) coding sequence. This has resulted in the identification of a growing number of recessive titinopathy patients. The aim of this study was to (1) characterize the causative genetic variants and clinical features of the largest cohort of recessive titinopathy patients reported to date and (2) to evaluate genotype-phenotype correlations in this cohort.

Perovskite and Conjugated Polymer Wrapped Semiconducting Carbon Nanotube Hybrid Films for High-Performance Transistors and Phototransistors.

Although organic-inorganic halide perovskites continue to generate considerable interest due to great potentials for various optoelectronic devices, there are some critical obstacles to practical applications, including lead toxicity, relatively low field-effect mobility, and strong hysteresis during operation. This paper proposes a universal approach to significantly improve mobility and operational stability with reduced dual-sweep hysteresis for perovskite-based thin film transistors (TFTs) by coupling low-dimensional lead-free perovskite material (CHCHNH)SnI (hereafter abbreviated as (PEA)SnI) with embedded conjugated polymer wrapped semiconducting carbon nanotubes (semi-CNTs). In (PEA)SnI/semi-CNT hybrid TFTs, semi-CNTs can provide highway-like transport paths, enabling smoother carrier transport with less trapping and scattering.

Interpreting Genetic Variants in Titin in Patients With Muscle Disorders.

Importance: Mutations in the titin gene (TTN) cause a wide spectrum of genetic diseases. The interpretation of the numerous rare variants identified in TTN is a difficult challenge given its large size.

Objective: To identify genetic variants in titin in a cohort of patients with muscle disorders.

Diagnostic anoctamin-5 protein defect in patients with ANO5-mutated muscular dystrophy.

Aims: Previously, detection of ANO5 protein has been complicated by unspecific antibodies, most of which have not identified the correct protein. The aims of the study were to specify ANO5 protein expression in human skeletal muscle, and to investigate if the ANO5 protein levels are affected by different ANO5 mutations in anoctaminopathy patients.

Methods: Four different antibodies were tested for ANO5 specificity.

CAPN3-mediated processing of C-terminal titin replaced by pathological cleavage in titinopathy.

Mutations in the extreme C-terminus of titin (TTN), situated in the sarcomeric M-band, cause tibial muscular dystrophy (TMD) and limb-girdle muscular dystrophy 2J (LGMD2J). The mutations ultimately cause a loss of C-terminal titin, including a binding site for the protease calpain 3 (CAPN3), and lead to a secondary CAPN3 deficiency in LGMD2J muscle. CAPN3 has been previously shown to bind C-terminal titin and to use it as a substrate in vitro.

Welander distal myopathy is caused by a mutation in the RNA-binding protein TIA1.

Objective: A study was undertaken to identify the molecular cause of Welander distal myopathy (WDM), a classic autosomal dominant distal myopathy.

Methods: The genetic linkage was confirmed and defined by microsatellite and single nucleotide polymorphism haplotyping. The whole linked genomic region was sequenced with targeted high-throughput and Sanger sequencing, and coding transcripts were sequenced on the cDNA level.

Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy.

Limb-girdle muscular dystrophy type 1D (LGMD1D) was linked to chromosome 7q36 over a decade ago, but its genetic cause has remained elusive. Here we studied nine LGMD-affected families from Finland, the United States and Italy and identified four dominant missense mutations leading to p.Phe93Leu or p.

Spanish MYH7 founder mutation of Italian ancestry causing a large cluster of Laing myopathy patients.

Laing myopathy is a distal myopathy caused by mutations in the tail of the slow beta-myosin heavy chain gene MYH7. A large cluster of patients belonging to different families, with Laing myopathy due to p.K1729del mutation, was found in the Safor region, Spain.

Four new Finnish families with LGMD1D; refinement of the clinical phenotype and the linked 7q36 locus.

The objective is to refine the clinical and morphological phenotype and the chromosomal region of interest, in the recently reported 7q36 linked autosomal dominant limb-girdle muscular dystrophy (LGMD1 D/E), by describing four new informative Finnish families. Examinations of the patients included serum CK, neurophysiological studies, cardiac and respiratory function examinations, muscle biopsies and muscle imaging. DNA samples were analyzed by genotyping.

MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy.

Objective: To describe a wide range of clinical and pathologic myopathic profiles associated with the p.K1729del mutation in the MYH7 gene, known to cause Laing distal myopathy.

Methods: A study conducted in the Safor region (Spain), setting of a large cluster of patients.

The enigma of 7q36 linked autosomal dominant limb girdle muscular dystrophy.

Introduction: Two families with autosomal dominant limb girdle muscular dystrophy (LGMD) have previously been linked to a locus on chromosome 7q36 10 years ago. The locus has been termed both LGMD1D and 1E, but because of lack of additional families to narrow down the linked region of interest, this disease has remained elusive.

Methods: A large Finnish family was clinically and genetically investigated.