ABSTRACT
A genotype-phenotype study based on the primary clinical features of adult myotonic dystrophy (DM) included 116 patients from 62 Italian pedigrees. A significant correlation between clinical severity and the number of repeats at the 3' untranslated region of the myotonin-protein kinase gene (MT-PK) was found. These results suggest that the CTG amplification is directly related to the myotonic dystrophy phenotype and provide important information on morbidity and prognosis in this disease.
Subject(s)
Mutation , Myotonic Dystrophy/genetics , Phenotype , Protein Serine-Threonine Kinases , Adolescent , Adult , Alleles , Base Sequence , Child , DNA/analysis , DNA/metabolism , Female , Gene Amplification , Humans , Italy , Male , Middle Aged , Molecular Sequence Data , Muscle Proteins/genetics , Myotonic Dystrophy/pathology , Myotonin-Protein Kinase , Protein Kinases/genetics , Repetitive Sequences, Nucleic AcidABSTRACT
The expression of myotonin-protein kinase (MT-PK) gene was studied in myotonic dystrophy (DM) muscle and normal controls using a polymerase chain reaction protocol to analyse the 3' intragenic p(CTG) polymorphism. Unaffected individuals show bi-allelic expression, while the sole wild-type allele was transcribed in DM muscle. Our findings support a gene dosage effect in the pathogenesis of the disease.
Subject(s)
Gene Expression Regulation, Enzymologic , Muscles/enzymology , Myotonic Dystrophy/genetics , Protein Kinases/genetics , Protein Serine-Threonine Kinases , RNA, Messenger/genetics , Adult , Alleles , Blotting, Southern , DNA/biosynthesis , Electrophoresis, Polyacrylamide Gel , Fetus/metabolism , Humans , Mutation , Myotonic Dystrophy/enzymology , Myotonin-Protein Kinase , Polymerase Chain Reaction , Polymorphism, Genetic , Protein Kinases/chemistry , RNA, Messenger/analysis , Transcription, GeneticABSTRACT
We report on linkage analysis and haplotype characterization in 40 Italian families with spinal muscular atrophy (SMA). The investigated loci included D5S6, D5S112, D5S39, and D5S76. No evidence of unlinked families was found. Thirty-two (80%) of the examined families were fully informative for prenatal diagnosis and carrier detection. The frequencies of individual alleles did not differ between SMA and normal chromosomes.
Subject(s)
Genetic Linkage , Muscular Atrophy, Spinal/diagnosis , Muscular Atrophy, Spinal/genetics , Adult , Alleles , Child , DNA/analysis , DNA/isolation & purification , DNA Probes , Gene Frequency , Genotype , Haplotypes , Humans , Lod Score , Polymorphism, Restriction Fragment LengthABSTRACT
Myotonic dystrophy results from expansion of a (CTG)n repeat at the 3' untranslated region of the myotonin-protein kinase gene. We show here the genomic analysis of 322 symptomatic patients with the cDNA-25 probe detecting disease specific EcoRI restriction fragments. The expansion was found in the majority of Italian and Spanish patients (92%). The implications of these results for the detection of symptomatic patients in southern Europe are discussed.
