Research Article Open Access

UNUSUAL SPECTRUM OF GENETIC PATHOLOGIES AND NOVEL MUTATIONS IN PWS AND AS PATIENTS DETECTED BY A WIDE CLUSTER OF METHODS

Livia Kotysova1, Robert Petrovic2 and Jan Chandoga2
  • 1 Faculty of Natural Sciences of Comenius University Bratislava, Slovakia
  • 2 Comenius University Faculty of Medicine and University Hospital Bratislava, Slovakia

Abstract

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 pattern analyses of the SNRPN exon 1/promoter region within the PWS/AS critical domain. Apart from unifying methylation-specific PCR and allele specific real-time PCR with melt-curve analysis as the fundamental methods for suspected diagnosis confirmation, we combined several specifically methods used to clarify the 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 atypical deletion that does not include common breakpoints, novel highly likely to be pathologic UBE3A mutation, uniparental heterodisomy together with partial isodisomy and epimutation without any deletions in the imprinting centre. We present genotype-phenotype correlation of all positive cases. In addition, we estimate the incidence for Slovakian population at 1 in 20,000 for PWS and 1 in 40,000 for AS.

OnLine Journal of Biological Sciences
Volume 14 No. 3, 2014, 218-229

DOI: https://doi.org/10.3844/ojbsci.2014.218.229

Submitted On: 18 August 2014 Published On: 12 November 2014

How to Cite: Kotysova, L., Petrovic, R. & Chandoga, J. (2014). UNUSUAL SPECTRUM OF GENETIC PATHOLOGIES AND NOVEL MUTATIONS IN PWS AND AS PATIENTS DETECTED BY A WIDE CLUSTER OF METHODS. OnLine Journal of Biological Sciences, 14(3), 218-229. https://doi.org/10.3844/ojbsci.2014.218.229

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Keywords

  • Prader-Willi and Angelman Syndromes
  • Unusual Cases
  • UBE3A Gene, 15q11.2-q13 Region’s Deletion Breakpoints