title: Imprinting centre deletions in two PWS families: implications for diagnostic testing and genetic counseling.
abstract: Prader-Willi syndrome (PWS) is a complex genetic syndrome involving imprinted genes on chromosome 15. It is usually sporadic, and very few affected siblings have been described. Here, we report the clinical and molecular findings in two families with a microdeletion affecting the chromosome 15 imprinting centre (IC). Carrier males have a 50% risk of having children with an imprinting defect leading to PWS, and in one of the two families, a father has two affected daughters. In the other family, diagnostic testing was confounded by the presence of a neutral microdeletion close to the IC. The silent transmission of PWS IC deletions through the female germline and the occurrence of neutral microdeletions close to the IC can impose considerable problems on diagnostic testing and genetic counselling in affected families.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Germany. karin.buiting@uni-essen.de
authors.forename: K
authors.initials: K
authors.lastname: Buiting
authors.forename: C
authors.initials: C
authors.lastname: Färber
authors.forename: P
authors.initials: P
authors.lastname: Kroisel
authors.forename: K
authors.initials: K
authors.lastname: Wagner
authors.forename: L
authors.initials: L
authors.lastname: Brueton
authors.forename: M E
authors.initials: ME
authors.lastname: Robertson
authors.forename: C
authors.initials: C
authors.lastname: Lich
authors.forename: B
authors.initials: B
authors.lastname: Horsthemke
mesh_terms: D000483:Alleles; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002884:Chromosomes, Human, Pair 15; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D005817:Genetic Counseling; D018392:Genomic Imprinting; D018095:Germ-Line Mutation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011218:Prader-Willi Syndrome / Q000175:diagnosis* / Q000235:genetics*; D012307:Risk Factors