25例基因拷贝数变异致罕见遗传病临床分析

目的 探讨基因拷贝数变异致罕见遗传病患儿的临床表现及基因拷贝数变异检测在罕见遗传病诊断中的价值。方法 回顾分析2013年2月至2021年2月就诊于中南大学湘雅医学院附属海口医院儿科的25例基因拷贝数变异致罕见遗传病患儿的临床表现，并将其分为染色体微缺失/微重复综合征组和单基因遗传病组，使用Fisher确切概率法统计患儿临床表型在两组出现频率的差异。结果 25例患儿中，男性12例（48.00%），女性13例（52.00%）；平均发病年龄为（1.20±2.24）岁；起病形式不同，急性起病7例（28.00%），慢性起病18例（72.00%）。25例患儿临床表型复杂多样，主要有12种。将其分为两组，分别为17例染色体微缺失/微重复综合征（68.00%）,8例单基因遗传病（32.00%）；“生长发育迟缓/智力低下”“面容异常”和“先天畸形”三种临床表型的差异在两组之间具有统计学意义。25例患儿中有23例（92.00%）首先行基因全外显子测序，未发现致病性点突变，进一步行基因拷贝数变异检测明确诊断；2例（8.00%）则直接行拷贝数变异检测明确诊断。结论 基因拷贝数变异致罕见遗传病大部分在婴幼儿时期...

Clinical analysis of 25 cases of rare genetic diseases caused by gene copy number variation

Objective To investigate the clinical manifestations of children with rare genetic diseases caused by gene copy number variation and the value of gene copy number variation detection in the diagnosis of rare genetic diseases. Methods The clinical manifestations of 25 children with rare genetic diseases caused by gene copy number variation who were treated in the Department of Pediatrics, The Affiliated Haikou Hospital of Xiangya Medical College, Central South University from February 2013 to February 2021 were retrospectively analyzed, and they were divided into chromosomal microdeletion/microduplication syndrome group and the single-gene genetic disease group, Fisher's exact probability method was used to count the differences in the frequency of clinical phenotypes between the two groups. Results Among the 25 children, there were 12 males (48.00%) and 13 females (52.00%); the average age of onset was （1.20±2.24） years old; the onset forms were different, with acute onset in 7 cases (28.00%) and chronic onset in 18 cases (72.00%). The clinical phenotypes of the 25 children were complex and diverse, mainly including 12 types. They were divided into two groups, including 17 cases of chromosomal microdeletion/microduplication syndrome (68.00%) and 8 cases of monogenic hereditary disorders (32.00%). Differences in the clinical phenotypes of "growth retardation/hypophrenia", "abnormal facial features" and "congenital malformations" were statistically significant between the two groups. In 23 of the 25 cases (92.00%), gene whole exon sequencing was performed first, and no pathogenic point mutation was found, and gene copy number variation was further tested to confirm the diagnosis. 2 cases (8.00%) were diagnosed by copy number variation test. Conclusions Most of the rare genetic diseases caused by gene copy number variation start in infancy and young children, and the incidence of males and females are roughly the same. It involves a variety of diseases and complex clinical phenotypes. The three clinical phenotypes "growth retardation/hypophrenia", "abnormal facial features" and "congenital malformations" in chromosomal microdeletion/microduplication syndrome with a high probability. Gene copy number variation detection is an important means of diagnosing rare genetic diseases, which can be used as a supplement to whole exome sequencing of genes, thereby improving the diagnostic level of rare genetic diseases to a certain extent.