Prader-Willi syndrome due to uniparental disomy in a patient with a balanced chromosomal translocation.
OBJECTIVE
In contrast to most human autosomal genes which are expressed biallelically, the expression of imprinted genes depends on the parental origin of the allele. Prader-Willi syndrome is a neurobehavioral disorder in which the expression of active paternal alleles of imprinted genes from chromosomal region 15q11-q13 is abolished by deletions, maternal uniparental disomy or imprinting defects. We report an unusual case of maternal uniparental disomy of chromosome 15 due to a balanced translocation t(8;15)(q24.1;q21.2) leading to Prader-Willi syndrome in a 3-year-old girl.


RESULTS
Cytogenetic investigation revealed a balanced translocation t(8;15)(q24.1;q21.2) in the patient and subsequently also in her unaffected mother. Fluorescence in situ hybridization analysis did not reveal any deletion of the PWS critical region, but methylation analysis of the SNRPN gene showed an abnormal methylation pattern indicating the absence of paternal chromosome 15. Microsatellite analysis of multiple loci and methylation-specific MLPA analysis confirmed maternal uniparental heterodisomy of chromosome 15 as the cause of PWS in the patient.


CONCLUSIONS
This example emphasizes the importance of uniparental disomy testing in pregnancies of carriers of chromosomal aberrations with participation of chromosomes carrying imprinted genes involved in human diseases.
Calounova
Gabriela
G
Institute of Biology and Medical Genetics, Charles University Second Medical School and University Hospital Motol, Prague, Czech Republic. gabriela.calounova@post.cz.
Novotna
Drahuse
D
Simandlova
Martina
M
Havlovicova
Markéta
M
Zumrová
Alena
A
Kocarek
Eduard
E
Sedlacek
Zdenek
Z
D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15; D002898:Chromosomes, Human, Pair 8; D020732:Cytogenetic Analysis; D019175:DNA Methylation; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018895:Microsatellite Repeats; D011218:Prader-Willi Syndrome / Q000235:genetics*; D014178:Translocation, Genetic; D024182:Uniparental Disomy / Q000235:genetics*