Publications by authors named "Sunitha Balaraju"
Congenital myasthenic syndromes (CMS) are a rare group of inherited disorders caused by gene defects associated with the neuromuscular junction and potentially treatable with commonly available medications such as acetylcholinesterase inhibitors and β2 adrenergic receptor agonists. In this study, we identified and genetically characterized the largest cohort of CMS patients from India to date. Genetic testing of clinically suspected patients evaluated in a South Indian hospital during the period 2014-19 was carried out by standard diagnostic gene panel testing or using a two-step method that included hotspot screening followed by whole-exome sequencing.
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- Microtubules play a crucial role in forming the cytoskeleton in neurons and other cells, and mutations in the gamma-tubulin complex have been associated with neurodevelopmental disorders.
- A Turkish family with two siblings exhibited developmental issues and brain malformations due to a homozygous mutation in the GCP2 protein, which affects its interaction with GCP3.
- Proteomic analyses revealed that this mutation disrupts proteins essential for cytoskeleton assembly and neuronal function, implicating GCP2 and the γ-tubulin complex in central nervous system development.
Article Synopsis
- A new neurodevelopmental condition linked to the TLK2 gene features mild delays in motor skills and language, along with distinct facial features.
- Most cases involve unique genetic changes (including truncating or missense variants) that lead to reduced TLK2 protein levels.
- A patient with a severe presentation, including cerebellar hypoplasia and West syndrome, was found to have a homozygous variant, suggesting that recessive mutations in TLK2 might also contribute to disease through different mechanisms.
Congenital myasthenic syndromes (CMS) are a clinically and genetically heterogeneous group of disorders caused by mutations which lead to impaired neuromuscular transmission. SLC25A1 encodes a mitochondrial citrate carrier, associated mainly with the severe neurometabolic disease combined D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA). We previously reported a single family with a homozygous missense variant in SLC25A1 with a phenotype restricted to relatively mild CMS with intellectual disability, but to date no additional cases of this CMS subtype had been reported.
View Article and Find Full Text PDFMuscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes.
View Article and Find Full Text PDFObjective: In this prospective study conducted over 2 years, 300 nonconsecutive cases of autosomal recessive limb girdle muscular dystrophies (AR-LGMD) were characterized, based on phenotypic features, biochemical findings, electrophysiological studies, muscle immunohistochemistry (IHC), and western blot (WB) analysis.
Methods: Muscle biopsy was performed in 280 index cases. 226 biopsies were subjected for IHC, and, 176 of these for WB analysis.
Article Synopsis
- - TCAP encoded telethonin is a 19 kDa protein crucial for anchoring titin in the sarcomere, and mutations in this protein are linked to LGMD2G, a rare muscle disorder that leads to muscle weakness and loss of mobility.
- - In a study involving 300 individuals with ARLGMD, researchers identified 8 cases of LGMD2G from 7 unrelated Dravidian families, characterized by symptoms like muscle weakness, scapular winging, and calf hypertrophy, along with a marked reduction of telethonin levels.
- - Genetic analysis uncovered two novel mutations in affected individuals that likely produce nonfunctional protein products, marking the first report from India highlighting the connection between TCAP and
Muscular dystrophies (MDs) and inflammatory myopathies (IMs) are debilitating skeletal muscle disorders characterized by common pathological events including myodegeneration and inflammation. However, an experimental model representing both muscle pathologies and displaying most of the distinctive markers has not been characterized. We investigated the cardiotoxin (CTX)-mediated transient acute mouse model of muscle degeneration and compared the cardinal features with human MDs and IMs.
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