Related Experiment Videos
A 34 bp deletion within TSC2 is a rare polymorphism, not a pathogenic mutation
Penelope S Roberts1, Vijaya Ramesh, Sandra Dabora
1Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Annals of Human Genetics
|December 4, 2003
Summary
A rare TSC2 gene deletion is not a cause of Tuberous Sclerosis (TSC) but may modify its symptoms. This genetic variation was found in unaffected parents, indicating it
Area of Science:
- Genetics
- Molecular Biology
- Medical Genetics
Background:
- Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by mutations in TSC1 or TSC2 genes.
- A specific 34 bp deletion in TSC2 has been previously reported.
Purpose of the Study:
- To investigate the role of a specific 34 bp deletion in TSC2 in the etiology and phenotype of Tuberous Sclerosis Complex (TSC).
- To determine if this deletion is a causative mutation or a polymorphism in TSC patients.
Main Methods:
- Screening of 800 TSC patients for mutations in TSC1 and TSC2.
- Genetic analysis of affected individuals and their unaffected parents.
- RT-PCR analysis of RNA samples to assess transcript integrity.
- Exclusion of parental mosaicism.
Main Results:
- The 34 bp deletion was identified in 4 out of 800 TSC patients, always inherited from an unaffected parent.
- RT-PCR showed the deletion allele produces approximately 50% normal TSC2 RNA transcript and 50% with intron 38 inclusion.
- No correlation was found between splicing extent and clinical status.
- Parental mosaicism was excluded.
Conclusions:
- The 34 bp deletion in TSC2 is a rare polymorphism, not a causative mutation for TSC.
- This polymorphism may potentially act as a modifier of the TSC phenotype.