Myotonic dystrophy: application of a novel triplet-repeat-primed-pcr approach to Turkish DM patients and molecular analysis of a large Turkish kindred with Von Hippel-Lindau disease

Abstract

Myotonic Dystrophy (DM) is an autosomal dominant neuromuscular disease with multisystemic effects. DM1 and DM2 are two clinically similar types of DM that are caused by different mutations on different genes. DM1, the more common form, is caused by an unstable CTG repeat expansion in the 3' UTR of the Myotonic Dystrophy Protein Kinase (DMPK) gene. In DM1, as a multisystemic disorder, several different systems are affected. The CTG region on the DMPK gene is highly polymorphic with 5-37 CTG repeats in the healthy population. Since there are several clinical similarities between DM1 and DM2, routine molecular diagnosis becomes very important in DM. In the framework of this study, a new Triplet-Repeat-Primed-PCR (TP-PCR) approach was established and applied to 117 suspected DM1 cases. Although the exact number of CTG repeats of highly expanded alleles cannot be determined by TP-PCR, we have proven that TP-PCR is a fast and reliable molecular diagnostic method that can also be used in future for other triplet repeat disorders. Von Hippel-Lindau (VHL) disease is an autosomal dominant condition that is characterized by the development of various benign and malignant tumors in different parts of the organisms. In this study, we investigated a large VHL family and identified the disease-causing mutation in exon 3 of the VHL gene, leading to a premature stop codon in the protein.