Prader-Willi syndrome resulting from an unbalanced translocation: Characterization by array comparative genomic hybridization

O. D. Klein, P. D. Cotter, D. G. Albertson, D. Pinkel, W. E. Tidyman, M. W. Moore, Katherine A Rauen

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)477-482
Number of pages6
JournalClinical Genetics
Volume65
Issue number6
DOIs
StatePublished - Jun 2004
Externally publishedYes

Fingerprint

Prader-Willi Syndrome
Comparative Genomic Hybridization
Monosomy
Chromosomes, Human, Pair 15
Chromosomes
snRNP Core Proteins
Mothers
Phenotype
Microcephaly
Cryptorchidism
Cytogenetic Analysis
Karyotype
Genetic Promoter Regions
Chromosome Aberrations
Methylation
Genes
Alleles
Polymerase Chain Reaction

Keywords

  • Array CGM
  • Chromosome 15
  • Chromosome 5
  • Microarray analysis
  • Prader-Willie syndrome
  • Unbalanced translocation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Prader-Willi syndrome resulting from an unbalanced translocation : Characterization by array comparative genomic hybridization. / Klein, O. D.; Cotter, P. D.; Albertson, D. G.; Pinkel, D.; Tidyman, W. E.; Moore, M. W.; Rauen, Katherine A.

In: Clinical Genetics, Vol. 65, No. 6, 06.2004, p. 477-482.

Research output: Contribution to journalArticle

Klein, O. D. ; Cotter, P. D. ; Albertson, D. G. ; Pinkel, D. ; Tidyman, W. E. ; Moore, M. W. ; Rauen, Katherine A. / Prader-Willi syndrome resulting from an unbalanced translocation : Characterization by array comparative genomic hybridization. In: Clinical Genetics. 2004 ; Vol. 65, No. 6. pp. 477-482.
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