title: A translocation breakpoint cluster disrupts the newly defined 3' end of the SNURF-SNRPN transcription unit on chromosome 15.
abstract: Balanced translocations affecting the paternal copy of 15q11--q13 are a rare cause of Prader-Willi syndrome (PWS) or PWS-like features. Here we report on the cytogenetic and molecular characterization of a de novo balanced reciprocal translocation t(X;15)(q28;q12) in a female patient with atypical PWS. The translocation breakpoints in this patient and two previously reported patients map 70-80 kb distal to the SNURF-SNRPN gene and define a breakpoint cluster region. The breakpoints disrupt one of several hitherto unknown 3' exons of this gene. Using RT--PCR we demonstrate that sequences distal to the breakpoint, including the recently identified C/D box small nucleolar RNA (snoRNA) gene cluster HBII-85 as well as IPW and PAR1, are not expressed in the patient. Our data suggest that lack of expression of these sequences contributes to the PWS phenotype.
authors.affiliation: Max-Planck Institut für Molekulare Genetik.
authors.forename: J
authors.initials: J
authors.lastname: Wirth
authors.forename: E
authors.initials: E
authors.lastname: Back
authors.forename: A
authors.initials: A
authors.lastname: Hüttenhofer
authors.forename: H G
authors.initials: HG
authors.lastname: Nothwang
authors.forename: C
authors.initials: C
authors.lastname: Lich
authors.forename: S
authors.initials: S
authors.lastname: Gross
authors.forename: C
authors.initials: C
authors.lastname: Menzel
authors.forename: A
authors.initials: A
authors.lastname: Schinzel
authors.forename: P
authors.initials: P
authors.lastname: Kioschis
authors.forename: N
authors.initials: N
authors.lastname: Tommerup
authors.forename: H H
authors.initials: HH
authors.lastname: Ropers
authors.forename: B
authors.initials: B
authors.lastname: Horsthemke
authors.forename: K
authors.initials: K
authors.lastname: Buiting
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D001324:Autoantigens / Q000235:genetics*; D001483:Base Sequence; D002871:Chromosome Banding; D019457:Chromosome Breakage / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D020732:Cytogenetic Analysis; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011218:Prader-Willi Syndrome / Q000235:genetics / Q000473:pathology; D011506:Proteins / Q000235:genetics*; D017411:Ribonucleoproteins, Small Nuclear; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D014960:X Chromosome / Q000235:genetics; D055517:snRNP Core Proteins
chemical_list: D001324:Autoantigens; D018076:DNA, Complementary; D009687:Nuclear Proteins; D011506:Proteins; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; C445239:SNURF protein, human; D055517:snRNP Core Proteins; D004247:DNA