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Prader–Willi syndrome resulting from an unbalanced translocation: characterization by array comparative genomic hybridization
Author(s) -
Klein OD,
Cotter PD,
Albertson DG,
Pinkel D,
Tidyman WE,
Moore MW,
Rauen KA
Publication year - 2004
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.0009-9163.2004.00261.x
Subject(s) - comparative genomic hybridization , uniparental disomy , genetics , biology , monosomy , chromosome 15 , genomic imprinting , chromosomal translocation , proband , karyotype , chromosome , dna methylation , gene , mutation , gene expression
Prader–Willi syndrome (PWS) is caused by lack of expression of paternally inherited genes on chromosome 15q11→15q13. Most cases result from microdeletions in proximal chromosome 15q. The remainder results from maternal uniparental disomy of chromosome 15, imprinting center defects, and rarely from balanced or unbalanced chromosome rearrangements involving chromosome 15. We report a patient with multiple congenital anomalies, including craniofacial dysmorphology, microcephaly, bilateral cryptorchidism, and developmental delay. Cytogenetic analysis showed a de novo 45,XY,der(5)t(5;15)(p15.2;q13), ‐15 karyotype. In effect, the proband had monosomies of 5p15.2→pter and 15pter→15q13. Methylation polymerase chain reaction analysis of the promoter region of the SNRPN gene showed only the maternal allele, consistent with the PWS phenotype. The proband's expanded phenotype was similar to other patients who have PWS as a result of unbalanced translocations and likely reflects the contribution of the associated monosomy. Array comparative genomic hybridization (array CGH) confirmed deletions of both distal 5p and proximal 15q and provided more accurate information as to the size of the deletions and the molecular breakpoints. This case illustrates the utility of array CGH in characterizing complex constitutional structural chromosome abnormalities at the molecular level.