title: Partial hexasomy for the Prader-Willi-Angelman syndrome critical region due to a maternally inherited large supernumerary marker chromosome.
abstract: Extra copies of the Prader-Willi-Angelman syndrome critical region (PWASCR) have been shown to have detrimental phenotypic effects depending on the parent of origin. Hexasomy for the PWASCR is rare; only 6 cases have been described to date. We report on a 15-year-old girl referred for developmental delay and seizures with a mosaic tricentric small marker chromosome (SMC) 15 identified by routine G-banding chromosome studies. C-banding and FISH confirmed the presence of three chromosome 15 centromeres as well as four copies of the PWASCR on the SMC in approximately 60% of interphase cells. Microsatellite genotyping documented maternal inheritance of the SMC, and methylation-sensitive multiplex ligation-dependent PCR amplification (MS-MLPA) showed that the extra copies of the PWASCR contained on the marker chromosome bear a methylation pattern similar to a normal maternal chromosome, implying maternal inheritance. These findings are consistent with the patient's phenotype as paternal inheritance of such a marker chromosome is thought to be benign. However, this patient's phenotype is the mildest described to date and may be a result of mosaicism for the SMC.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. hoppmanchaney.nicole@mayo.edu
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Hoppman-Chaney
authors.forename: D Brian
authors.initials: DB
authors.lastname: Dawson
authors.forename: Lai
authors.initials: L
authors.lastname: Nguyen
authors.forename: Sunanda
authors.initials: S
authors.lastname: Sengupta
authors.forename: Kara
authors.initials: K
authors.lastname: Reynolds
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McPherson
authors.forename: Gopalrao
authors.initials: G
authors.lastname: Velagaleti
mesh_terms: D000293:Adolescent; D017204:Angelman Syndrome / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009030:Mosaicism; D009035:Mothers; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics* / Q000473:pathology