TY - JOUR
T1 - Clinical and genetic study of a family with a paternally inherited 15q11-q13 duplication
AU - Marini, Carla
AU - Cecconi, Antonella
AU - Contini, Elisa
AU - Pantaleo, Marilena
AU - Metitieri, Tiziana
AU - Guarducci, Silvia
AU - Giglio, Sabrina
AU - Guerrini, Renzo
AU - Genuardi, Maurizio
PY - 2013/6
Y1 - 2013/6
N2 - Interstitial chromosome 15q11-q13 duplications are associated with developmental delay, behavioral problems and additional manifestations, including epilepsy. In most affected individuals the duplicated chromosome is maternally derived, whereas paternal inheritance is more often associated with a normal phenotype. Seizures have not been described in patients with paternal dup 15q11-q13. We describe a family with five individuals in three generations with a paternally-inherited 15q11-q13 duplication, four of whom exhibited abnormal phenotypic characteristics, including seizures. The 18-year-old female proband presented with moderate intellectual disability, obesity, and epilepsy. Her brother manifested learning disability and behavioral problems. They both inherited the 15q11-q13 dup from their father who had a normal phenotype. Their paternal uncle and grandfather also had the duplication and were reported to have had seizures. Array-CGH and MLPA analyses showed that the duplication included the TUBGCP5, CYFIP1, MKRN3, MAGEL2, NDN, SNRPN, UBE3A, ATP10A, GABRB3, GABRA5, GABRG3, and OCA2 genes. This report provides evidence for intrafamilial phenotypic variability of paternal dup 15q11-q13, ranging from normal to intellectual disability and seizures, and potentially expanding the phenotype of paternal 15q11-q13 interstitial duplications.
AB - Interstitial chromosome 15q11-q13 duplications are associated with developmental delay, behavioral problems and additional manifestations, including epilepsy. In most affected individuals the duplicated chromosome is maternally derived, whereas paternal inheritance is more often associated with a normal phenotype. Seizures have not been described in patients with paternal dup 15q11-q13. We describe a family with five individuals in three generations with a paternally-inherited 15q11-q13 duplication, four of whom exhibited abnormal phenotypic characteristics, including seizures. The 18-year-old female proband presented with moderate intellectual disability, obesity, and epilepsy. Her brother manifested learning disability and behavioral problems. They both inherited the 15q11-q13 dup from their father who had a normal phenotype. Their paternal uncle and grandfather also had the duplication and were reported to have had seizures. Array-CGH and MLPA analyses showed that the duplication included the TUBGCP5, CYFIP1, MKRN3, MAGEL2, NDN, SNRPN, UBE3A, ATP10A, GABRB3, GABRA5, GABRG3, and OCA2 genes. This report provides evidence for intrafamilial phenotypic variability of paternal dup 15q11-q13, ranging from normal to intellectual disability and seizures, and potentially expanding the phenotype of paternal 15q11-q13 interstitial duplications.
KW - Chromosome 15q11-q13
KW - Duplication
KW - Imprinting
KW - Intellectual disability
KW - Interstitial
KW - Parental origin
KW - Seizures
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U2 - 10.1002/ajmg.a.35907
DO - 10.1002/ajmg.a.35907
M3 - Article
C2 - 23633446
AN - SCOPUS:84878250289
VL - 161
SP - 1459
EP - 1464
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 6
ER -