HGNC Approved Gene Symbol: IPW
Cytogenetic location: 15q11.2 Genomic coordinates (GRCh38) : 15:25,116,545-25,122,476 (from NCBI)
By direct selection of expressed sequences from the Prader-Willi syndrome (PWS; 176270) smallest region of deletion overlap on paternal chromosome 15q11-q13, Wevrick et al. (1994) isolated a gene they showed to be expressed exclusively from the paternal allele in lymphoblasts and fibroblasts. The gene, designated 'imprinted gene in the Prader-Willi syndrome region' (IPW), is spliced and polyadenylated but encodes a polypeptide of only 45 amino acids. They showed that the transcript is cytoplasmic, as is the imprinted H19 gene (103280) on chromosome 11, and that it is widely expressed in adult and fetal tissues. By YAC contig analysis, Wevrick et al. (1994) placed IPW about 150 kb distal to SNRPN (182279) and about 50 kb proximal to the breakpoint of a translocation defining the distal end of the PWS critical region and the proximal end of the Angelman syndrome (105830) region. The authors observed that PWS patients with 15q11-q13 deletions do not express IPW, whereas expression was normal in Angelman syndrome patients. Wevrick et al. (1994) speculated that the IPW may function as an RNA (not unlike the XIST (314670) and H19 transcripts) and that it may play a role in the imprinting process.
Wevrick and Francke (1997) cloned a mouse gene, designated Ipw, that has sequence similarity to a part of IPW and is located in the conserved homologous region of mouse chromosome 7. The Ipw cDNA also contains no long open reading frame, is alternatively spliced, and contains multiple copies of a 147 bp repeat, arranged in a head-to-tail orientation, that are interrupted by the insertion of an intracisternal A particle sequence. Ipw is expressed predominantly in brain. They could show that expression of Ipw in an interspecies F1 animal was limited to the paternal allele. Because of all of these striking similarities, Wevrick and Francke (1997) proposed that Ipw is the murine homolog of IPW, a prime candidate for involvement in the cause of Prader-Willi syndrome.
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 (182279) and defined a breakpoint cluster region. The breakpoints disrupted one 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 and PAR1 (600161), were not expressed in the patient. The authors suggested that lack of expression of these sequences may contribute to the PWS phenotype.
Wevrick, R., Francke, U. An imprinted mouse transcript homologous to the human imprinted in Prader-Willi syndrome (IPW) gene. Hum. Molec. Genet. 6: 325-332, 1997. [PubMed: 9063754] [Full Text: https://doi.org/10.1093/hmg/6.2.325]
Wevrick, R., Kerns, J. A., Francke, U. Identification of a novel paternally expressed gene in the Prader-Willi syndrome region. Hum. Molec. Genet. 3: 1877-1882, 1994. [PubMed: 7849716] [Full Text: https://doi.org/10.1093/hmg/3.10.1877]
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]