Uniparental Disomy of Chromosome 15 in Two Cases by Chromosome Microarray: A Lesson Worth Thinking

Area of Science:

• Genetics
• Molecular Biology
• Neurogenetics

Background:

• Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurogenetic disorders.
• These conditions are typically caused by deletions in the 15q11q13 chromosomal region.
• Uniparental disomy (UPD) of chromosome 15 is a less common genetic cause.

Purpose of the Study:

• To report on two children with PWS/AS caused by rare mixed segmental uniparental heterodisomy (heteroUPD) and isodisomy (isoUPD) of chromosome 15.
• To investigate the underlying genetic mechanisms and phenotype-genotype correlations of this rare UPD type.
• To assess the diagnostic limitations of chromosome microarray (CMA) for imprinting disorders like PWS/AS.

Main Methods:

• Analysis of two pediatric cases presenting with PWS/AS phenotypes.
• Utilized molecular genetic methods beyond chromosome microarray (CMA).
• Included methylation analysis and STR marker analysis for UPD detection.

Main Results:

• Identified two cases of PWS/AS resulting from mixed segmental heteroUPD 15 and isoUPD 15.
• Chromosome microarray (CMA) failed to detect these specific UPD events.
• Alternative molecular genetic techniques successfully diagnosed the mixed UPD 15.
• Phenotype-genotype correlations were established for the identified cases.

Conclusions:

• Mixed segmental heteroUPD 15 and isoUPD 15 can cause PWS/AS phenotypes.
• Chromosome microarray (CMA) may misdiagnose imprinting disorders like PWS/AS.
• Methylation analysis and STR marker analysis are crucial supplementary methods for diagnosing UPD in PWS/AS patients.