Identification of a Novel Intronic Mutation in VMA21 Associated with a Classical Form of X-Linked Myopathy with Autophagy.

Introduction VMA21 -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. Method Here, we describe a case of genetically confirmed VMA21 -associated myopathy with clinical, histopathological, and imaging features with a list of known VMA21 mutations. Results A 29-year-old man had the onset of symptoms at 18 years of age with features of proximal lower limb weakness. Muscle magnetic resonance imaging showed the preferential involvement of vasti and adductor magnus. A biopsy of the left quadriceps femoris showed features of autophagic vacuolar myopathy with vacuoles containing granular eosinophilic materials. In targeted next-generation sequencing, hemizygous mutation in the 3' splice site of intron 2 of the VMA21 gene (c.164-7 T > A) was identified and confirmed the diagnosis of X-linked myopathy with excessive autophagy. Conclusion This report expands the phenotypic and genotypic profile of VMA21 -related myopathy, with a yet unreported mutation in India.

Disease Progression and Associations of Microvascular Complications in Diabetic Patients: A Study From South India.

Diabetes mellitus (DM) is a chronic metabolic disease characterized by inappropriately elevated blood glucose levels. If not treated at the early stage, it can lead to complications like diabetic retinopathy (DR) and diabetic nephropathy (DN) which are often associated with severe morbidity and mortality. This study was designed to identify the prevalence of retinopathy and nephropathy in diabetic patients and also to determine the correlation between DR and DN. In this cross-sectional study, a total of 84 diabetic patients (Male: Female- 53:31) were included. The mean age at presentation was 54.06 ± 9.85 years. Among them, 28% of patients had a duration of diabetes of < 5 years. Nearly 42% and 30% of patients had diabetes between 5-10 years, and more than 10 years respectively. At the time of presentation to us, a total of 42.8% of patients had a combination of nephropathy and retinopathy, 40.4% of patients had only retinopathy, and 16.6% of patients with only nephropathy. Among patients with nephropathy and microalbuminuria, only 5.9% had DR ranging from mild to a moderate degree and none had severe DR. In patients with macroalbuminuria, 26.2% had moderate to severe DR. Microvascular complications are more prevalent in diabetics with disease progression. Microalbuminuria is a marker for retinopathy and these patients require ophthalmic evaluation at the earliest. Early recognition and management of these, can reduce the occurrence of complications as well as disease progression, thus reducing the related mortality.

Disease Progression and Mutation Pattern in a Large Cohort of LGMD R1/LGMD 2A Patients from India.

Calpainopathy is caused by mutations in the CAPN3 . There is only one clinical and genetic study of CAPN3 from India and none from South India. A total of 72 (male[M]:female [F] = 34:38) genetically confirmed probands from 72 independent families are included in this study. Consanguinity was present in 54.2%. The mean age of onset and duration of symptoms are 13.5 ± 6.4 and 6.3 ± 4.7 years, respectively. Positive family history occurred in 23.3%. The predominant initial symptoms were proximal lower limb weakness (52.1%) and toe walking (20.5%). At presentation, 97.2% had hip girdle weakness, 69.4% had scapular winging, and 58.3% had contractures. Follow-up was available in 76.4%, and 92.7% were ambulant at a mean age of 23.7 ± 7.6 years and duration of 4.5 years, remaining 7.3% became wheelchair-bound at 25.5 ± 5.7 years of age (mean duration = 13.5 ± 4.6), 4.1% were aged more than 40 years (duration range = 5-20). The majority remained ambulant 10 years after disease onset. Next-generation sequencing (NGS) detected 47 unique CAPN3 variants in 72 patients, out of which 19 are novel. Missense variants were most common occurring in 59.7% (homozygous = 29; Compound heterozygous = 14). In the remaining 29 patients (40.3%), at least one suspected loss of function variant was present. Common recurrent variants were c.2051-1G > T and c.2338G > C in 9.7%, c.1343G > A, c.802-9G > A, and c.1319G > A in 6.9% and c.1963delC in 5.5% of population. Large deletions were observed in 4.2%. Exon 10 mutations accounted for 12 patients (16.7%). Our study highlights the efficiency of NGS technology in screening and molecular diagnosis of limb-girdle muscular dystrophy with recessive form (LGMDR1) patients in India.