Mutation Spectrum of Tuberous Sclerosis Complex Patients in Indian Population.

Tuberous sclerosis complex (TSC) is a multiorgan disorder characterized by formation of hamartomas and broad phenotypic spectrum including seizures, mental retardation, renal dysfunction, skin manifestations and brain tubers. It is inherited in an autosomal dominant pattern, caused due to mutation in either or genes. Seizures are one of the major presenting symptoms of TSC that helps in early diagnosis. The present study describes the mutation spectrum in and genes in TSC patients and their association with neurocognitive-behavioral phenotypes. Ninety-eight TSC patients were enrolled for TSC genetic testing after detailed clinical and neurobehavioral assessment. Large genomic rearrangement testing was performed by multiplex ligation-dependent probe amplification (MLPA) technique for all cases and Sanger sequencing was performed for MLPA negative cases. Large rearrangements were identified in approximately 1% in and 14.3% in genes. The present study observed the presence of duplications in two (2%) cases, both involving contiguous genes which to the best of our knowledge is reported for the first time. 8.1% of small variants were identified in the gene and 85.7% in gene, out of which 23 were novel variations and no variants were found in six (6.1%) cases. This study provides a representative picture of the distribution of variants in the and genes in Indian population along with the detailed assessment of neurological symptoms. This is the largest cohort study from India providing an overview of comprehensive clinical and molecular spectrum.