ABSTRACT
AIM: To perform a clinical-genealogical and molecular genetic analysis of X-linked spinal-bulbar amyotrophy (Kennedy's disease) in the Sakha Republic (Yakutia). MATERIAL AND METHODS: Six patients, aged from 30 to 60 years, from 4 unrelated Yakut families registered in the Republican genetics registry of hereditary and congenital abnormalities of the Sakha Republic were studied. The average age of onset was 45.1±4.4 years. A clinical-genealogical and molecular genetic methods were used. RESULTS AND CONCLUSION: The prevalence of spinal-bulbar amyotrophy Kennedy in the Republic of Sakha (Yakutia) is 1.3 per 100 thousand, among Yakut men is 2.8 per 100 thousand. Clinical manifestations of the disease in the patients included in the study were similar to those described previously in the literature. Patients underwent molecular genetic diagnosis in exon 1 of the androgen receptor (AR) gene. All of them carried the allele with more than 38 CAG repeats. There was an inverse correlation between the age at disease onset and the number of CAG-repeats. A method of DNA diagnosis of Kennedy's disease with visualization on an agarose gel has been introduced in genetic testing.
Subject(s)
Bulbo-Spinal Atrophy, X-Linked , Adult , DNA , Genetic Testing , Humans , Male , Middle AgedABSTRACT
The genetic variability of the DMPK locus has been studied in relation to six SNP markers (rs2070736, rs572634, rs1799894, rs527221, rs915915, and rs10415988) in Yakuts with myotonic dystrophy (MD) in the Yakut population and in populations of northern Eurasia. Significant differences were observed in the allele frequencies between patients and a population sample of Yakuts for three SNP loci (rs915915, rs1799894, and rs10415988) associated with a high chance of disease manifestation. The odds ratios (OR) of MD development in representatives of the Yakut population for these three loci were 2.59 (95% CI, p = 0,004), 4.99 (95% CI, p = 0.000), and 3.15 (95% CI, p = 0.01), respectively. Haplotype TTTCTC, which is associated with MD, and haplotype GTCCTT, which was observed only in Yakut MD patients (never in MD patients of non-Yakut origin), were revealed. A low level of variability in the locus of DMRK gene in Yakuts (H(e) = 0.283) compared with other examined populations was noted. An analysis of pairwise genetic relationships between populations revealed their significant differentiation for all the examined loci. In addition, a low level of differentiation in territorial groups of Yakut populations (F(ST) = 0.79%), which was related to the high subdivision of the northern Eurasian population (F(ST) = 11.83%), was observed.
Subject(s)
Myotonic Dystrophy/genetics , Myotonin-Protein Kinase/genetics , Polymorphism, Single Nucleotide , Asian People/genetics , Haplotypes , Humans , Myotonic Dystrophy/ethnology , SiberiaABSTRACT
The clinical-genealogic and molecular-genetic investigation of oculopharyngeal muscular dystrophy (OPMD) in the Republic of Sakha (Yakutia) was performed. It was investigated 33 unrelated Yakut families with 38 patients and 2 russian families with 2 patients and 59 their healthy relatives as well. The high clinical polymorphism of disease was found in patients with OPMD. The mutation in exon 1 of the PABPN1 gene resulting in the expansion of GCG-repeats up to 10 is revealed. Using direct sequencing of the PABPN1 gene in 17 families (16 Yakut, 1 Russian), we identified a type of this mutation as an insertion of 4 GCG-repeats. Frequency of OPMD in the Yakut population is 1:11 680 that is 10-20 times higher comparing to european populations. This is a first report on the patients with OPMD from the Republic of Sakha with diagnosis confirmed by molecular-genetic analysis.
