Prader-Willi syndrome is caused by disruption of the SNRPN gene.

A Prader-Willi syndrome patient is described who has a de novo balanced translocation, (4;15)(q27;q11.2)pat, with breakpoints lying between SNRPN exons 2 and 3. Parental-origin studies indicate that there is no uniparental disomy and no apparent deletion. This patient expresses ZNF127, SNRPN exons 1 and 2, IPW, and D15S227E (PAR1) but does not express either SNRPN exons 3 and 4 or D15S226E (PAR5), as assayed by reverse transcription-PCR, of peripheral blood cells. Methylation studies showed normal biparental patterns of inheritance of loci DN34/ZNF127, D15S63, and SNRPN exon 1. Results for this patient and that reported by Sun et al. support the contention that an intact genomic region and/or transcription of SNRPN exons 2 and 3 play a pivotal role in the manifestations of the major clinical phenotype in Prader-Willi syndrome.