Genetic abnormalities in Prader-Willi syndrome and lessons from mouse models.
Prader-Willi syndrome is a multigenic disorder with developmental and neurobehavioural abnormalities. There are multiple genetic causes, although all ultimately involve the loss of paternally derived gene expression of chromosome region 15q11-q13. Multiple imprinted genes expressed only from the paternal allele have been identified in the specific region of human chromosome 15q associated with Prader-Willi syndrome and in the syntenic mouse chromosome 7C region, including a novel polycistronic gene (SNURF-SNRPN) that encodes two independent proteins. The latter genetic locus may play a key role in Prader-Willi syndrome and the evolution of imprinting in this domain, because it is uniquely involved with mutations in the imprinting process and balanced translocations in this syndrome. Indeed, based on the co-localization of SNURF and SNRPN within the imprinting control region critical to Prader-Willi syndrome, evolutionary arguments would suggest that this genetic locus is a prime candidate for mutations producing the failure-to-thrive phenotype of neonates with this syndrome and of corresponding mouse models. Hence, the SNURF-SNRPN gene may encode a paternally derived postnatal growth factor.
Nicholls
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Department of Genetics, Case Western Reserve University School of Medicine and Center for Human Genetics, University Hospitals of Cleveland, Ohio 44106-4955, USA. rxn19@po.cwru.edu
Ohta
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Gray
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D017204:Angelman Syndrome / Q000235:genetics; D000818:Animals; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004195:Disease Models, Animal; D018392:Genomic Imprinting; D006801:Humans; D051379:Mice; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics*; D014178:Translocation, Genetic