Detection of Mosaicisms in Tuberous Sclerosis
Dr. rer. nat. Karin Mayer
In 15-20% of all patients with a clinical diagnosis of TSC no genetic cause can be detected applying the standard diagnostic methods. Some of these patients have a genetic mosaicism where the proportion of cells with a mutation in the TSC1 or TSC2 gene in the analyzed tissue lies below the detection limit of Sanger sequencing. Other mutations lie within regulatory regions of the TSC genes. By analyzing the whole genomic region of both TSC genes with a coverage of 1,000x it is possible to detect mosaicism with a proportion of < 5% and intronic mutations which lie beyond intron/exon boundaries.
The whole genomic region of the TSC genes is amplified by long-range PCR and analyzed by next generation sequencing (NGS) with a minimum coverage of 1,000x.
Mayer et al, Eur J Hum Genet 20 (Supp1): Abstract P11.132, 287 (2012) / Qin et al, Hum Genet 127:573 (2010) / Mayer K et al, Biochim Biophys Acta 1502:495 (2000)