A paternal deletion of MKRN3, MAGEL2 and NDN does not result in Prader-Willi syndrome.
The Prader-Willi syndrome (PWS) is caused by a 5-6 Mbp de novo deletion on the paternal chromosome 15, maternal uniparental disomy 15 or an imprinting defect. All three lesions lead to the lack of expression of imprinted genes that are active on the paternal chromosome only: MKRN3, MAGEL2, NDN, C15orf2, SNURF-SNRPN and more than 70 C/D box snoRNA genes (SNORDs). The contribution to PWS of any of these genes is unknown, because no single gene mutation has been described so far. We report on two patients with PWS who have an atypical deletion on the paternal chromosome that does not include MKRN3, MAGEL2 and NDN. In one of these patients, NDN has a normal DNA methylation pattern and is expressed. In another patient, the paternal alleles of these genes are deleted as the result of an unbalanced translocation 45,X,der(X)t(X;15)(q28;q11.2). This patient is obese and mentally retarded, but does not have PWS. We conclude that a deficiency of MKRN3, MAGEL2 and NDN is not sufficient to cause PWS.
Kanber
Deniz
D
Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany.
Giltay
Jacques
J
Wieczorek
Dagmar
D
Zogel
Corinna
C
Hochstenbach
Ron
R
Caliebe
Almuth
A
Kuechler
Alma
A
Horsthemke
Bernhard
B
Buiting
Karin
K
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007621:Karyotyping; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011218:Prader-Willi Syndrome / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012261:Ribonucleoproteins; D044767:Ubiquitin-Protein Ligases; C510822:MAGEL2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins; C445239:SNURF protein, human; C069766:necdin; C119425:MKRN3 protein, human