摘要目的:探讨 HERC2基因变异所致智力障碍伴发育迟缓1个家系的遗传学特征。 方法:选取于2020年5—7月在大理大学第一附属医院就诊的1个智力障碍伴发育迟缓的患儿家系3代共10人为研究对象。收集该家系先证者的临床资料及家系成员患病情况，应用全外显子组测序技术对先证者进行致病基因筛选，采用Sanger测序对可疑致病基因进行家系验证。根据美国遗传学与基因组学（American College of Medical Genetics and Genomics，ACMG）学会的基因变异解读标准与指南对可疑致病基因突变位点进行致病性分类。结果:先证者男，12岁，因“发育迟缓9年，智力障碍3个月”就诊，表现为身材矮小，无故自语自笑，眼神对周围环境回避，韦氏智力测验提示智力水平低下。先证者弟弟有类似智力障碍伴发育迟缓等表现，余家系成员正常。全外显子组测序结果显示先证者携带 HERC2基因c.7675A>G位点纯合突变，Sanger测序显示其弟弟携带同样的 HERC2基因c.7675A>G位点纯合突变，其余家系成员携带相同的 HERC2基因c.7675A>G位点杂合突变。根据ACMG指南判定该基因位点突变为临床意义未明。 结论:HERC2基因c.7675A>G位点突变可能是导致该家系智力障碍伴发育迟缓的遗传学基础。

abstractsObjective:To explore the genetic characteristics of a family with intellectual impairment and developmental delay caused by HERC2 gene mutation. Methods:A total of 10 individuals from a 3-generation family of a child with intellectual disability and developmental delay who was treated at the First Affiliated Hospital of Dali University from May to July 2020 were recruited. Clinical data of probands from the family and the illness status of family members were collected. Whole exome sequencing technology was used to screen for pathogenic genes in probands, meanwhile, Sanger sequencing was conducted to verify the family of suspected pathogenic genes. According to the American College of Medical Genetics and Genomics (ACMG) genetic variation interpretation standards and guidelines, pathogenicity classification of suspected pathogenic gene mutation sites was performed.Results:The patient, male, 12-year old, presented with the clinical characteristics of "developmental delay for 9 years and intellectual disability for 3 months". The patient was characterized by a short stature, spontaneous laughter and avoidance of the surrounding environment. One younger brother has symptoms similar to intellectual impairment with developmental delay, while the remaining family members are normal. The Wechsler Intelligence Test of the child indicates a low level of intelligence. The whole exome sequencing results showed that the proband carried a homozygous mutation at the c.7675A>G site of the HERC2 gene, while Sanger sequencing showed that the younger brother carried the same homozygous mutation at the c.7675A>G site of the HERC2 gene. The other family members carried the same heterozygous mutation at the c.7675A>G site of the HERC2 gene. According to the ACMG guidelines, the mutation at this gene site is clinically unclear. Conclusion:The mutation at the c.7675A>G locus of HERC2 gene is the genetic basis of mental retardation with stunting in this family.