title: A 28-kb deletion spanning D15S63 (PW71) in five families: a rare neutral variant?
abstract: Methylation analysis with probe PW71 (D15S63) is an established procedure to test patients suspected of having Prader-Willi syndrome or Angelman syndrome. Using this test, we have identified a 28-kb deletion spanning D15S63 in five independent families. Sequence analysis revealed identical breakpoints in all the families. The haplotype data are compatible with a common ancestral origin of the deletion in at least two families. The deletion was not found in 1, 000 unrelated controls. Although the deletion maps within the imprinting-center region, neither maternal nor paternal inheritance of the deletion appears to affect imprinting in proximal 15q. We conclude that the deletion is a rare neutral variant that can lead to false-positive results in the PW71-methylation test.
authors.affiliation: Institut für Humangenetik, Universitätsklinkum Essen, 45122 Essen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Buiting
authors.forename: B
authors.initials: B
authors.lastname: Dittrich
authors.forename: B
authors.initials: B
authors.lastname: Dworniczak
authors.forename: I
authors.initials: I
authors.lastname: Lerer
authors.forename: D
authors.initials: D
authors.lastname: Abeliovich
authors.forename: S
authors.initials: S
authors.lastname: Cottrell
authors.forename: I K
authors.initials: IK
authors.lastname: Temple
authors.forename: J F
authors.initials: JF
authors.lastname: Harvey
authors.forename: C
authors.initials: C
authors.lastname: Lich
authors.forename: S
authors.initials: S
authors.lastname: Gross
authors.forename: B
authors.initials: B
authors.lastname: Horsthemke
mesh_terms: D000293:Adolescent; D000328:Adult; D017204:Angelman Syndrome / Q000175:diagnosis / Q000235:genetics; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage / Q000235:genetics; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D019175:DNA Methylation; D005189:False Positive Reactions; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics; D005858:Germany; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D010375:Pedigree; D020161:Physical Chromosome Mapping; D011218:Prader-Willi Syndrome / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D005819:Genetic Markers