UNUSUAL SPECTRUM OF GENETIC PATHOLOGIES AND NOVEL MUTATIONS IN PWS AND AS PATIENTS DETECTED BY A WIDE CLUSTER OF METHODS
| Autor: | Robert Petrovic, Livia Kotysova, Ján Chandoga |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Genetics
congenital hereditary and neonatal diseases and abnormalities education.field_of_study Population Locus (genetics) Single-nucleotide polymorphism Biology Uniparental Heterodisomy General Biochemistry Genetics and Molecular Biology Chromosome 15 Exon UBE3A General Agricultural and Biological Sciences Genomic imprinting education |
| Zdroj: | OnLine Journal of Biological Sciences. 14:218-229 |
| ISSN: | 1608-4217 |
| DOI: | 10.3844/ojbsci.2014.218.229 |
| Popis: | Prader-Willi and Angelman syndromes are clinically distinct neurodevelopmental genetic disorders that map to 15q11.2-q13 locus. The common phenotypes are attributable to loss of expression of parentally specific imprinted genes inside this region, where the gene function is dependent on parental origin. Initial diagnosis was proved for the years by methylation p attern analyses of the SNRPN exon 1/promoter region within the PWS/AS critical domain. Apart from unifying methylation-specific PCR and allele specific re altime PCR with melt-curve analysis as the fundamental methods for suspected diagnosis confirmation, we combined several specific methods used to clarify t he molecular cause. In our study we had identified and genotyped 24 PWS and AS patients from 450 suspected. Applied cluster of methods - microsatellite analysis of SNPs within the chromosome 15, Methylation-specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA) and UBE3A gene sequence analysis, enable us to determined at ypical deletion that does not include common breakpoints, novel hig hly likely to be causative UBE3A mutation, uniparental heterodisomy together with partial isodisomy and ep imutation without any deletions in the imprinting centre. We present genotype-phenotype correlation o f all positive cases. In addition, we estimate the incidence for Slovak population at 1 in 20,000 for PWS and 1 in 40,000 for AS. |
| Databáze: | OpenAIRE |
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