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Prader-Willi syndrome

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. - defects in necdin may be a cause of the Prader-Willi syndrome. Clinical manifestations: The Prader-Willi syndrome (PWS) is a disorder characterized by - neonatal hypotonia with poor suck - mild to moderate mental retardation - short stature - obesity beginning after 3 yr of age - hypogonadism - small hands & feet - characteristic facial features Laboratory: - see ARUP consult [3]

Related

Prader-Willi/Angelman syndrome genotyping small nuclear ribonucleoprotein associated protein N (SmN) [tissue-specific slicing factor] (SnRPN)

General

genetic syndrome (multisystem disorder)

Database Correlations

OMIM correlations

References

  1. Woodage et al Genomics 19(1):170-2, 1994
  2. Saitoh Am J Med Genetics 52(2):158-63, 1994
  3. 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