Prader-Willi syndrome

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Genetics

the Prader-Willi syndrome (PWS) & the Angelman syndrome (AS) are 2 clinically distinct disorders caused by a differential parental origin of chromosome 15q11-q13 deletions.
both also can result from uniparental disomy (inheritance of both copies of chromosome 15 from only one parent)
loss of the paternal copy of 15q11-q13, whether by deletion or maternal uniparental disomy, leads to PWS, whereas a maternal deletion or paternal uniparental disomy leads to AS.

differential modification in expression of certain mammalian genes dependent upon parental origin is known as genomic imprinting, & AS & PWS represent the best examples of this phenomenon in humans
although molecular mechanisms of genomic imprinting are unknown, DNA methylation has been proposed to play a role in the imprinting process.

the small nuclear ribonucleoprotein polypeptide N (SmN) is the 1st expressed gene identified in the PWS critically deleted region.
it is a polymorphic protein monoallelically expressed in fetal brain & heart & in adult brain
analysis of maternal DNA & SmN cDNA indicate that the maternal allele of SmN is not expressed in fetal brain & heart
maternal imprinting of SmN suggests that paternal absence of SmN is responsible for the PWS phenotype
SmN is thought to be involved in splicing of pre-mRNA
closely related protein, SmB/B', is constitutively expressed in all tissues except the brain, where SmN is predominantly expressed.

The Prader-Willi syndrome (PWS) is a disorder characterized by

↑ Woodage et al Genomics 19(1):170-2, 1994
↑ Saitoh Am J Med Genetics 52(2):158-63, 1994
↑ ^3.0 ^3.1 ARUP Consult: Angelman Syndrome and Prader-Willi Syndrome The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/prader-willi-syndrome
Angelman Syndrome and Prader-Willi Syndrome Testing https://arupconsult.com/ati/angelman-syndrome-and-prader-willi-syndrome-testing