title: Mutation and polymorphism analysis of TSC1 and TSC2 genes in Indian patients with tuberous sclerosis complex.
abstract: OBJECTIVE
  To find the mutation and polymorphism spectrum of TSC1 and TSC2 genes in patients affected with tuberous sclerosis complex from the Indian population.
  
  
  METHODS
  All coding exons and promoter regions of both TSC genes were screened for mutations and polymorphisms in 24 TSC families using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing techniques.
  
  
  RESULTS
  A single previously known mutation, c.2111_2112delAT was identified in the TSC1 gene. A total of 11 mutations were identified in the TSC2 gene. Of these, seven mutations, c.137_138delGA, c.2070delC, c.2087_2088insAA, c.3080T>C (p.L1027P), c.648+1G>A, c.3131+1G>A and c.5034C>G were novel. The remaining four mutations, c.4544_4547delACAA, c.1941_1942insT, c.1831C>T (p.R611W) and c.1832G>A (p.R611Q) had been reported previously in other populations. The novel mutation, c.137_138delGA was predicted to result in the production of a very small tuberin protein of 64 amino acids lacking all seven functional domains. In addition, we also detected three and 10 polymorphisms in the TSC1 and TSC2 genes respectively. DNA sequence analysis of promoter regions of both TSC genes in 24 families did not show any variation.
  
  
  CONCLUSIONS
  This is the first molecular genetic study of TSC in an Indian population. A total of 12 mutations were detected in 24 Indian TSC families in TSC genes. All except one mutation were detected in the TSC2 gene. No variation was found in the promoter regions of either gene. As observed in the western and Japanese populations, the mutations were scattered across the TSC2 gene.
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
authors.forename: M
authors.initials: M
authors.lastname: Ali
authors.forename: S C
authors.initials: SC
authors.lastname: Girimaji
authors.forename: M
authors.initials: M
authors.lastname: Markandaya
authors.forename: A K
authors.initials: AK
authors.lastname: Shukla
authors.forename: S
authors.initials: S
authors.lastname: Sacchidanand
authors.forename: A
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000595:Amino Acid Sequence; D018389:Codon, Nonsense; D017353:Gene Deletion; D005820:Genetic Testing; D006801:Humans; D007194:India; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D022821:RNA Splice Sites / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D014402:Tuberous Sclerosis / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D022821:RNA Splice Sites; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins