Prader-Willi syndrome
Genetics
The Prader-Willi syndrome (PWS) & the Angelman syndrome (AS) are two clinically distinct disorders that are caused by a differential parental origin of chromosome 15q11-q13 deletions. Both also can result from uniparental disomy (the 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. The gene for MAGE-like protein 2 is within this region.
The 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 the molecular mechanisms of genomic imprinting are unknown, DNA methylation has been postulated to play a role in the imprinting process.
The small nuclear ribonucleoprotein polypeptide N (SmN) is the first 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 and 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. A 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
More general terms
Additional terms
- Prader-Willi/Angelman syndrome genotyping
- small nuclear ribonucleoprotein associated protein N (SmN) [tissue-specific slicing factor] (SnRPN)
References
- ↑ 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
Database
- OMIM: https://mirror.omim.org/entry/176270
- OMIM: https://mirror.omim.org/entry/600161
- OMIM: https://mirror.omim.org/entry/600162
- OMIM: https://mirror.omim.org/entry/182279
- OMIM: https://mirror.omim.org/entry/602117
- OMIM: https://mirror.omim.org/entry/601491
- OMIM: https://mirror.omim.org/entry/605436