Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother
Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother
复制标题
DOI：
10.1038/ejhg.2011.244
复制
发表时间：
2012-05-01
影响因子：
5.2
通讯作者：
Betancur, Catalina
中科院分区：
文献类型：
--
作者：
Tabet, Anne-Claude;Pilorge, Marion;Betancur, Catalina
染色体16p的着丝粒周区富含节段性复制，易于通过非等位基因同源重组进行重排。最近在染色体16P上描述了几个重复的拷贝数变异。16p11.2重排(29.5-30.1 Mb)与自闭症、智力残疾(ID)和其他神经发育障碍有关。另一种可识别但不常见的16p11.2p12.2(21.4到28.5-30.1Mb)微缺失综合征已在6名ID患者中被描述，而标准细胞遗传学和荧光原位杂交技术研究的明显相互重复已在3名自闭症谱系障碍患者中被报道。在此，我们报道了一个有三个患有自闭症的男孩的多重家庭，其中两个同卵双胞胎携带着8.95Mb(21.28-30.23Mb)的重复16p11.2p12.2重复序列，其特征是单核苷酸多态阵列，包括16p11.2和16p11.2p12.2区域。这对双胞胎表现出自闭症、严重的ID和畸形特征，包括三角脸、深陷的眼睛、巨大而突出的鼻梁和修长的身材。大哥表现为自闭症、轻度ID、早发性肥胖和正常的头面部特征，并携带较小的重叠的16p11.2微缺失847kb(28.40-29.25Mb)，遗传自他看起来健康的父亲。包含SH2B1基因的这个区域的反复缺失最近在早发性肥胖症和与表型变异相关的神经发育障碍的个体中被报道。我们讨论了该家族中两种不同的16p染色体重排的临床和遗传学意义，并认为父亲的16p11.2缺失易于在双胞胎子女中形成重复。《欧洲人类遗传学杂志》(2012年)20540546；doi：10.1038/ejhg.2011.244；2012年1月11日在线发布
The pericentromeric region of chromosome 16p is rich in segmental duplications that predispose to rearrangements through non-allelic homologous recombination. Several recurrent copy number variations have been described recently in chromosome 16p. 16p11.2 rearrangements (29.5-30.1 Mb) are associated with autism, intellectual disability (ID) and other neurodevelopmental disorders. Another recognizable but less common microdeletion syndrome in 16p11.2p12.2 (21.4 to 28.5-30.1 Mb) has been described in six individuals with ID, whereas apparently reciprocal duplications, studied by standard cytogenetic and fluorescence in situ hybridization techniques, have been reported in three patients with autism spectrum disorders. Here, we report a multiplex family with three boys affected with autism, including two monozygotic twins carrying a de novo 16p11.2p12.2 duplication of 8.95 Mb (21.28-30.23 Mb) characterized by single-nucleotide polymorphism array, encompassing both the 16p11.2 and 16p11.2p12.2 regions. The twins exhibited autism, severe ID, and dysmorphic features, including a triangular face, deep-set eyes, large and prominent nasal bridge, and tall, slender build. The eldest brother presented with autism, mild ID, early-onset obesity and normal craniofacial features, and carried a smaller, overlapping 16p11.2 microdeletion of 847 kb (28.40-29.25 Mb), inherited from his apparently healthy father. Recurrent deletions in this region encompassing the SH2B1 gene were recently reported in early-onset obesity and in individuals with neurodevelopmental disorders associated with phenotypic variability. We discuss the clinical and genetic implications of two different 16p chromosomal rearrangements in this family, and suggest that the 16p11.2 deletion in the father predisposed to the formation of the duplication in his twin children. European Journal of Human Genetics (2012) 20, 540-546; doi:10.1038/ejhg.2011.244; published online 11 January 2012