Expert Reviews in Molecular Medicine

 



Review Article

Prader–Willi syndrome: clinical genetics, cytogenetics and molecular biology


Douglas C. Bittel a1 and Merlin G. Butler a1c1
a1 Section of Medical Genetics and Molecular Medicine, Children's Mercy Hospitals and Clinics; and University of Missouri-Kansas City School of Medicine, 2401 Gillham Rd, Kansas City, MO 64108, USA.

Abstract

Prader–Willi syndrome (PWS) is a neurodevelopmental disorder that arises from lack of expression of paternally inherited genes known to be imprinted and located in the chromosome 15q11-q13 region. PWS is considered the most common syndromal cause of life-threatening obesity and is estimated at 1 in 10 000 to 20 000 individuals. A de novo paternally derived chromosome 15q11-q13 deletion is the cause of PWS in about 70% of cases, and maternal disomy 15 accounts for about 25% of cases. The remaining cases of PWS result either from genomic imprinting defects (microdeletions or epimutations) of the imprinting centre in the 15q11-q13 region or from chromosome 15 translocations. Here, we describe the clinical presentation of PWS, review the current understanding of causative cytogenetic and molecular genetic mechanisms, and discuss future directions for research.


Key Words: Prader–Willi syndrome (PWS); epigenetic; imprinting; gene expression; obesity; maternal disomy; chromosome 15q11-q13 deletion; genetic subtypes.

Correspondence:
c1 Section of Medical Genetics and Molecular Medicine, Children's Mercy Hospitals and Clinics; and University of Missouri-Kansas City School of Medicine, 2401 Gillham Rd, Kansas City, MO 64108, USA. Tel: +1 816 234 3290; Fax: +1 816 346 1378; E-mail: mgbutler@cmh.edu