Purpose: We set out to develop a publicly available tool that could accurately diagnose spinal muscular atrophy (SMA) in exome, genome or panel sequencing datasets aligned to a GRCh37, GRCh38, or T2T reference genome.
Methods: The SMA Finder algorithm detects the most common genetic causes of SMA by evaluating reads that overlap the c.840 position of the SMN1 and SMN2 paralogs.
Introduction: GNE myopathy is a rare slowly progressive adult-onset distal myopathy with autosomal recessive inheritance. It has distinctive features of quadriceps sparing with preferential anterior tibial involvement. Most patients eventually become wheelchair bound by 10-20 years after onset.
View Article and Find Full Text PDFIntroduction: Amyotrophic lateral sclerosis (ALS) is characterized by motor, cognitive, and behavioral impairment. There is a paucity of evidence about the cognitive/behavioral features of ALS patients from India. We aimed to investigate the cognitive/behavioral profile of ALS spectrum disorders in the Indian context.
View Article and Find Full Text PDFIntroduction: Nuclear envelopathies occur due to structural and/or functional defects in various nuclear envelope proteins such as lamin A/C and lamin related proteins. This study is the first report on the phenotype-genotype patterns of nuclear envelopathy-related muscular dystrophies from India.
Methods: In this retrospective study, we have described patients with genetically confirmed muscular dystrophy associated with nuclear envelopathy.
Background: Congenital myopathies (CMs) are a diverse group of inherited muscle disorders with broad genotypic and phenotypic heterogeneity. While the literature on CM is available from European countries, comprehensive data from the Indian subcontinent is lacking.
Objectives: This study aims to describe the clinical and histopathological characteristics of a cohort of genetically confirmed CMs from India and attempts to do phenotype-genotype correlation.
Background: Congenital myasthenic syndromes (CMS) are a group of inherited neuromuscular junction (NMJ) disorders arising from gene variants encoding diverse NMJ proteins. Recently, the VAMP1 gene, responsible for encoding the vesicle-associated membrane protein 1 (VAMP1), has been associated with CMS.
Methods: This study presents a characterization of five new individuals with VAMP1-related CMS, providing insights into the phenotype.
Solve-RD is a pan-European rare disease (RD) research program that aims to identify disease-causing genetic variants in previously undiagnosed RD families. We utilised 10-fold coverage HiFi long-read sequencing (LRS) for detecting causative structural variants (SVs), single nucleotide variants (SNVs), insertion-deletions (InDels), and short tandem repeat (STR) expansions in extensively studied RD families without clear molecular diagnoses. Our cohort includes 293 individuals from 114 genetically undiagnosed RD families selected by European Rare Disease Network (ERN) experts.
View Article and Find Full Text PDF-related myopathy is one of the rare forms of slowly progressive myopathy observed in males. Till now, there have been only a handful of reports, mainly from Europe and America, and two reports from India. Here, we describe a case of genetically confirmed -associated myopathy with clinical, histopathological, and imaging features with a list of known VMA21 mutations.
View Article and Find Full Text PDFRecessive desminopathies are rare and often present as severe early-onset myopathy. Here we report a milder phenotype in three unrelated patients from southern India (2 M, 1F) aged 16, 21, and 22 years, who presented with childhood-onset, gradually progressive, fatigable limb-girdle weakness, ptosis, speech and swallowing difficulties, without cardiac involvement. Serum creatine kinase was elevated, and repetitive nerve stimulation showed decrement in all.
View Article and Find Full Text PDFBackground: Peripheral neuropathies in mitochondrial disease are caused by mutations in nuclear genes encoding mitochondrial proteins, or in the mitochondrial genome. Whole exome or genome sequencing enable parallel testing of nuclear and mtDNA genes, and it has significantly advanced the genetic diagnosis of inherited diseases. Despite this, approximately 40% of all Charcot-Marie-Tooth (CMT) cases remain undiagnosed.
View Article and Find Full Text PDFBackground: Electrocardiography (ECG) remains an excellent screening tool for cardiac assessment in Duchenne muscular dystrophy (DMD), but an accurate interpretation requires comparison with age-matched healthy controls.
Objective: We examined various ECG parameters in children with DMD, in comparison with age-matched controls.
Methods: Standard 12-lead ECG tracings of serial patients were screened for quality and selected.
Background: DM1 is a multisystem disorder caused by expansion of a CTG triplet repeat in the 3' non-coding region of DMPK. Neuropsychological consequences and sleep abnormalities are important associations in DM1.
Objective: To describe the clinical phenotype, disease progression and characterize the sleep alterations and cognitive abnormalities in a sub-set of patients.
Spinal muscular atrophy (SMA) is a genetic disorder that causes progressive degeneration of lower motor neurons and the subsequent loss of muscle function throughout the body. It is the second most common recessive disorder in individuals of European descent and is present in all populations. Accurate tools exist for diagnosing SMA from genome sequencing data.
View Article and Find Full Text PDFBackground And Objectives: Distal myopathies are a heterogeneous group of primary muscle disorders with recessive or dominant inheritance. is a muscle-specific adenylosuccinate synthase isoform involved in adenine nucleotide synthesis. Recessive pathogenic variants in the gene located in chromosome 14q32.
View Article and Find Full Text PDFCharcot-Marie-Tooth disease 4H(CMT4H) is an autosomal recessive demyelinating form of CMT caused by FGD4/FRABIN mutations. CMT4H is characterized by early onset and slowly progressing motor and sensory deficits in the distal extremities, along with foot deformities. We describe a patient with CMT4H who presented with rapidly progressing flaccid quadriparesis during the postpartum period, which improved significantly with steroid therapy.
View Article and Find Full Text PDFBackground: Hirayama disease (HD) is a cervical compressive myelopathy. Anterior cervical discectomy and fusion (ACDF) is identified as the best surgical approach. We evaluated surgical outcomes and factors influencing ACDF in HD.
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