Balanced translocation 46,XY,t(2;15)(q37.2;q11.2) associated with atypical Prader-Willi syndrome.
The lack of normally active paternal genes in 15q11-q13, as an outcome of either a paternal deletion or maternal disomy, accounts for >95% of all patients with Prader-Willi syndrome. Other mechanisms, including imprinting mutations and unbalanced translocations involving pat 15q11-q13, have been described elsewhere. In this study, we present a patient with a rare balanced, de novo translocation-46,XY,t(2;15)(q37.2;q11.2)-involving breakage within the Prader-Willi/Angelman syndrome region of the paternal homologue, without an apparent deletion. The patient demonstrated several manifestations of the Prader-Willi syndrome but was clinically atypical. Cytogenetic and molecular studies of this case demonstrated the translocation breakpoint to be between SNRPN and IPW, with mRNA expression of SNRPN and PAR-5 but absence of IPW and PAR-1 expression. These results suggest that disruption of either IPW expression or a nearby gene by an upstream break may contribute to the Prader-Willi syndrome phenotype and that expression of SNRPN or other upstream genes is responsible for other aspects of the classical Prader-Willi syndrome phenotype.
Conroy
J M
JM
Department of Genetics and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, OH 44106-9959, USA.
Grebe
T A
TA
Becker
L A
LA
Tsuchiya
K
K
Nicholls
R D
RD
Buiting
K
K
Horsthemke
B
B
Cassidy
S B
SB
Schwartz
S
S
D000818:Animals; D001324:Autoantigens / Q000235:genetics; D002675:Child, Preschool; D002871:Chromosome Banding; D019457:Chromosome Breakage; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D006224:Cricetinae; D019175:DNA Methylation; D005220:Fathers; D015870:Gene Expression; D018392:Genomic Imprinting; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D051741:Kruppel-Like Transcription Factors; D008297:Male; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics* / Q000473:pathology; D011494:Protein Kinases; D015183:Restriction Mapping; D017411:Ribonucleoproteins, Small Nuclear; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D055517:snRNP Core Proteins
D001324:Autoantigens; D051741:Kruppel-Like Transcription Factors; C490820:PEG3 protein, human; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; D014157:Transcription Factors; D055517:snRNP Core Proteins; D011494:Protein Kinases