Alternative titles; symbols
HGNC Approved Gene Symbol: PWAR1
Cytogenetic location: 15q11.2 Genomic coordinates (GRCh38) : 15:25,135,642-25,138,053 (from NCBI)
To determine the molecular basis of Prader-Willi syndrome (PWS; 176270) and Angelman syndrome (AS; 105830), Sutcliffe et al. (1994) isolated novel transcripts from chromosome 15q11-q13. They found that 2 novel transcripts, PAR1 and PAR5 (600162), were paternally expressed in cultured cells, along with SNRPN (182279), thereby defining a large imprinted transcriptional domain.
By analysis of a YAC contig, Sutcliffe et al. (1994) mapped the PAR1 gene within 300 kb telomeric to the SNRPN gene on chromosome 15q11-q13.
Sutcliffe et al. (1994) found that in 2 sibs with PWS and a third sporadic case, small deletions removed a differentially methylated CpG island containing a newly described 5-prime exon, designated alpha, of SNRPN, and caused loss of expression of the imprinted PAR1, PAR5, and SNRPN transcripts and altered methylation over hundreds of kilobases. (Sequences previously designated as exon 1 of SNRPN had been found, in fact, to lie approximately 12 kb telomeric of exon alpha, the true first exon of the gene.) The smallest PWS deletion was familial and was asymptomatic when transmitted through the mother. Sutcliffe et al. (1994) interpreted their data as indicating the presence of a paternal imprinting control region near exon alpha.
Balanced translocations affecting the paternal copy of 15q11-q13 are a rare cause of Prader-Willi syndrome (PWS) or PWS-like features. Wirth et al. (2001) reported 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 2 previously reported patients mapped 70 to 80 kb distal to the SNURF-SNRPN gene and defined a breakpoint cluster region. The breakpoints disrupted 1 of several previously unknown 3-prime exons of this gene. RT-PCR experiments demonstrated that sequences distal to the breakpoint, including the C/D box small nucleolar RNA (snoRNA) gene cluster HBII-85 (SNORD116-1; 605436), as well as IPW (601491) and PAR1, were not expressed in the patient. The authors suggested that lack of expression of these sequences may contribute to the PWS phenotype.
Sutcliffe, J. S., Nakao, M., Christian, S., Orstavik, K. H., Tommerup, N., Ledbetter, D. H., Beaudet, A. L. Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region. Nature Genet. 8: 52-58, 1994. [PubMed: 7987392] [Full Text: https://doi.org/10.1038/ng0994-52]
Wirth, J., Back, E., Huttenhofer, A., Nothwang, H.-G., Lich, C., Gross, S., Menzel, C,, Schinzel, A., Kioschis, P., Tommerup, N., Ropers, H.-H., Horsthemke, B., Buiting, K. A translocation breakpoint cluster disrupts the newly defined 3-prime end of the SNURF-SNRPN transcription unit on chromosome 15. Hum. Molec. Genet. 10: 201-210, 2001. [PubMed: 11159938] [Full Text: https://doi.org/10.1093/hmg/10.3.201]