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Partial hexasomy for the Prader–Willi–Angelman syndrome critical region due to a maternally inherited large supernumerary marker chromosome
Author(s) -
HoppmanChaney Nicole L.,
Dawson D. Brian,
Nguyen Lai,
Sengupta Sunanda,
Reynolds Kara,
McPherson Elizabeth,
Velagaleti Gopalrao
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33483
Subject(s) - marker chromosome , angelman syndrome , biology , genetics , small supernumerary marker chromosome , chromosome 15 , multiplex ligation dependent probe amplification , chromosome , autosome , karyotype , gene , exon
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. © 2010 Wiley‐Liss, Inc.