Author/Editor     Medica, Igor
Title     Genetic analysis of myotonic dystrophy in Croatian Istria
Translated title     Genetska analiza miotonične distrofije v hrvaški Istri
Type     monografija
Place     Ljubljana
Publisher     Medicinska fakulteta
Publication year     1997
Volume     str. 77
Language     eng
Abstract     Myotonic dystrophy, a neuromuscular disorder with the involvement of other organ systems, is one of the most prevalent inherited disorders. The molecular mechanism underlying myotonic dystrophy phenotype is the expansion of (CTG)n motif in the 3' untranslated region of the myotonin protein kinase gene. The discovery of the molecular etiology of the disease enables a definitive diagnosis, more reliable prevalence estimation and explanation of some population genetics theories, and provides the answer to the problem of the preservation of the mutated gene. The estimated prevalence rate of myotonic dystrophy in Croatin Istria, established in this study is 18.1/100,000. We consider this high prevalence to be due to patients' ascertainment through multiple sources and to the direct molecular analysis as a precise diagnostic test which enables the inclusion of atypical patients in the prevalence rate estimation. To test the founder effect, as a possible explanation for the high prevalence of myotonic dystrophy in Istria, we performed genealogical reconstruction of Istrian families, followed by direct and indirect molecular investigations of patients. We conclude that the gihg prevalence of myotonic dystrophy in Istria cannot be explained by the founder effect. Myotonic dystrophy in its severe form is known to diminish reproductive fitness, therefore it has the tendency to extinction from population. As no de novo mutations are known for this disease, it could be the consequence of one unique ancestral mutation. To explain the preservation of myotonic dystrophy in population, two hypotheses were tested. First, we tested the hypothesis about the segregation distortion in transmission of myotonic dystrophy mutation. Our results do not support the meiotic drive mechanism with the preferential transmission of the mutated allele. (Abstract tuncated at 2000 characters).
Descriptors     MYOTONIA ATROPHICA
EPIDEMIOLOGY, MOLECULAR
DNA
PEDIGREE
PREVALENCE
CATARACT
POLYMERASE CHAIN REACTION
BLOTTING, SOUTHERN
ELECTROMYOGRAPHY
POLYMORPHISM (GENETICS)
ALLELES
HAPLOTYPES