Clinical and Genetic Study of a Family With a Paternally Inherited 15q11-q13 Duplication
Clinical and Genetic Study of a Family With a Paternally Inherited 15q11-q13 Duplication
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DOI：
10.1002/ajmg.a.35907
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发表时间：
2013-06-01
影响因子：
2
通讯作者：
Genuardi, Maurizio
中科院分区：
文献类型：
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作者：
Marini, Carla;Cecconi, Antonella;Genuardi, Maurizio
间质染色体15 q11-q13重复与发育迟缓、行为问题和其他表现（包括癫痫）相关。在大多数受影响的个体中，重复的染色体是母系来源的，而父系遗传更经常与正常表型相关。在父系dup 15 q11-q13的患者中没有描述癫痫发作。我们描述了一个家族，三代五个人与父系遗传的15 q11-q13重复，其中四人表现出异常的表型特征，包括癫痫发作。18岁的女性先证者表现为中度智力残疾、肥胖和癫痫。她的兄弟表现出学习障碍和行为问题。他们都遗传了15 q11-q13 dup从他们的父亲谁具有正常的表型。他们的叔叔和祖父也有这种重复，并据报道患有癫痫发作。Array-CGH和MLPA分析表明，重复包括TUBGCP 5、CYFIP 1、MKRN 3、MAGEL 2、NDN、SNRPN、UBE 3A、ATP 10A、GABRB 3、GABRA 5、GABRG 3和OCA 2基因。本报告提供了父系dup 15 q11-q13家族内表型变异的证据，范围从正常到智力残疾和癫痫发作，并可能扩大父系15 q11-q13间质重复的表型。(C)2013 Wiley Periodicals，Inc.
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. (C) 2013 Wiley Periodicals, Inc.