Prader-Willi syndrome resulting from an unbalanced translocation: characterization by array comparative genomic...

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• Prader-Willi syndrome (PWS) is a genetic disorder typically caused by the absence of paternally inherited genes on chromosome 15q11-15q13.
• Common causes include microdeletions, maternal uniparental disomy, or imprinting defects on chromosome 15.

Observation:

• A patient presented with multiple congenital anomalies, including craniofacial dysmorphia, microcephaly, bilateral cryptorchidism, and developmental delay.
• Cytogenetic analysis revealed a de novo translocation, resulting in monosomies for 5p15.2-pter and 15pter-15q13.
• Methylation analysis confirmed the PWS phenotype by showing only the maternal allele for the SNRPN gene.

Findings:

• The patient's phenotype was consistent with PWS but expanded, suggesting contributions from the additional chromosomal deletions.
• Array comparative genomic hybridization (array CGH) precisely identified deletions in distal 5p and proximal 15q, detailing molecular breakpoints.
• This case demonstrates PWS resulting from a complex unbalanced translocation involving chromosomes 5 and 15.

Implications:

• Array CGH is a valuable tool for characterizing complex constitutional chromosomal abnormalities at a molecular level.
• Understanding these complex rearrangements aids in better defining the PWS phenotype and its genetic underpinnings.
• This finding expands the spectrum of genetic causes for Prader-Willi syndrome and associated developmental issues.