Transmitted duplication of 8p23.1-8p23.2 associated with speech delay, autism and learning difficulties
Transmitted duplication of 8p23.1-8p23.2 associated with speech delay, autism and learning difficulties
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DOI：
10.1038/ejhg.2008.133
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发表时间：
2009-01-01
影响因子：
5.2
通讯作者：
Barber, John C. K.
中科院分区：
文献类型：
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作者：
Glancy, Mary;Barnicoat, Angela;Barber, John C. K.
已报道有伴有和不伴有明显临床表型的8p远端重复，且其通常与不同寻常的结构复杂性程度相关。在此，我们介绍在一名有语言发育迟缓且被诊断为ICD - 10自闭症的儿童中确定的8p23.1 - 8p23.2重复。在其患有癫痫和学习问题的母亲中也发现了相同的重复。综合运用细胞遗传学、荧光原位杂交（FISH）、微卫星、多重连接依赖式探针扩增（MLPA）和寡核苷酸阵列比较基因组杂交（oaCGH）分析表明，该重复在3539893和10323426碱基对之间至少延伸6.8Mb。这个区间包含32个新基因和41个已知基因，其中目前只有小头畸形相关基因（MCPH1）是自闭症的一个可能的候选基因。重复区域的远端断点中断了8p23.2中的CSMD1基因，中间断点位于8p23.1中的MSRA和RP1L1基因之间。提出在一条正常的和多态性倒位的8号染色体之间发生染色体间插入来解释这种重复的起源。需要对8p远端进一步定位的失衡进行研究，以确定该家族表型中的自闭症成分是由许多基因的累积失衡还是单个易感基因的剂量失衡所导致。
Duplications of distal 8p with and without significant clinical phenotypes have been reported and are often associated with an unusual degree of structural complexity. Here, we present a duplication of 8p23.1-8p23.2 ascertained in a child with speech delay and a diagnosis of ICD-10 autism. The same duplication was found in his mother who had epilepsy and learning problems. A combination of cytogenetic, FISH, microsatellite, MLPA and oaCGH analysis was used to show that the duplication extended over a minimum of 6.8Mb between 3 539 893 and 10 323 426 bp. This interval contains 32 novel and 41 known genes, of which only microcephalin (MCPH1) is a plausible candidate gene for autism at present. The distal breakpoint of the duplicated region interrupts the CSMD1 gene in 8p23.2 and the medial breakpoint lies between the MSRA and RP1L1 genes in 8p23.1.An interchromosomal insertion between a normal and polymorphically inverted chromosome 8 is proposed to explain the origin of this duplication. Further mapped imbalances of distal 8p are needed to determine whether the autistic component of the phenotype in this family results from the cumulative imbalance of many genes or dosage imbalance of an individual susceptibility gene.