Molecular and clinical spectrum of type 1 myotonic dystrophy

Abstract

Myotonic dystrophy type 1 is a chronic, slowly progressing, inherited multisystemic autosomal-dominant disease, caused by expansion of CTG repeats in DMPK gene. The aim of present study was to analyze the molecular expansion in DM1 families and in normal individuals and to establish its relationships with disease. Clinically suspected 30 subjects (from 29 families) of DM1, 75 family members and 400 normal individuals were included in the study. Molecular diagnosis of CTG repeat expansion was performed by Myotonic Dystrophy Short PCR (MDSP) and Triplet primed-PCR (TP-PCR) and followed fragment analysis on ABI-310 Genetic Analyzer. SPSS version 16 and Pearson correlation coefficient were used for statistical analysis. All 30 patients had CTG repeat expansion pattern, correlated well with clinical phenotypes of DM1. Among 75, nine family members were permutated, while sixty six were normal. The allele frequency to repeat no. 5, 9–13 constituted approximate 80% of all 15 distributed allele (3–29) in normal individuals of DM1 families. Among, 400 normal individuals, the allele frequency to repeat number 5, 9–12, and 14–15 constituted approximate 85% out of 23 distributed allele (3–29). The expanded CTG repeat significantly correlated with age at onset, myotonia, wasting, weakness, hypersomnia, abnormal nerve conduction, clinical score and muscular disability rating scale. MDSP and TP-PCR could be successfully used for the identification of repeat expansion in normal individuals and in DM1 families. The finding is helpful not only for laboratory physicians performing tests and making molecular diagnosis, but also for clinicians diagnosing and counselling patients with variable onset and systemic involvement.