PDF(Pubmed)
Abstract：
This research analyzes the clinical data, whole-exome sequencing results, and in vitro minigene functional experiments of a child with developmental delay and intellectual disability. The male patient, aged 4, began experiencing epileptic seizures at 3 months post-birth and has shown developmental delay. Rehabilitation training was administered between the ages of one and two. There were no other significant family medical histories. Through comprehensive family exome genetic testing, a hemizygous variant in the 11th exon of the OPHN1 gene was identified in the affected child: c.1025 + 1G > A. Family segregation analysis confirmed the presence of this variant in the patient\'s mother, which had not been previously reported. According to the ACMG guidelines, this variant was classified as a likely pathogenic variant. In response to this variant, an in vitro minigene functional experiment was designed and conducted, confirming that the mutation affects the normal splicing of the gene\'s mRNA, resulting in a 56 bp retention on the left side of Intron 11. It was confirmed that OPHN1: c.1025 + 1G > A is the pathogenic cause of X-linked intellectual disabilities in the child, with clinical phenotypes including developmental delay and seizures.
摘要：
这项研究分析了临床数据，全外显子组测序结果,以及发育迟缓和智力障碍儿童的体外小基因功能实验。男病人,4岁，出生后3个月开始出现癫痫发作，并表现出发育迟缓。在1至2岁之间进行康复训练。没有其他重要的家庭病史。通过全面的家族外显子组基因检测,在受影响的儿童中鉴定出OPHN1基因第11外显子的半合子变异：c.1025+1G>A.家庭隔离分析证实了患者母亲中存在这种变异，以前没有报道过。根据ACMG指南,该变异被归类为可能的致病变异.作为对这种变体的回应，设计并进行了体外小基因功能实验，证实突变影响基因mRNA的正常剪接，导致在Intron11的左侧保留56bp。已证实OPHN1：c.1025+1G>A是儿童X连锁智力障碍的致病原因，临床表型包括发育迟缓和癫痫发作。
