TY - JOUR
T1 - Partial hexasomy for the Prader-Willi-Angelman syndrome critical region due to a maternally inherited large supernumerary marker chromosome
AU - Hoppman-Chaney, Nicole L.
AU - Dawson, D. Brian
AU - Nguyen, Lai
AU - Sengupta, Sunanda
AU - Reynolds, Kara
AU - McPherson, Elizabeth
AU - Velagaleti, Gopalrao
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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 amarker 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.
AB - 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 amarker 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.
KW - Hexasomy
KW - Prader-Willi-Angelman syndrome critical region
KW - Supernumerary marker chromosome 15
KW - Tricentric
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U2 - 10.1002/ajmg.a.33483
DO - 10.1002/ajmg.a.33483
M3 - Article
C2 - 20602489
AN - SCOPUS:77955296124
VL - 152
SP - 2034
EP - 2038
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 8
ER -