染色体微阵列分析技术对16p11.2综合征的诊断及遗传学分析

Diagnosis and genetic analysis of 16p11.2 syndrome by chromosome microarray analysis technology

目的探索16p11.2微缺失/微重复综合征患者的临床症状和染色体微阵列技术(CMA)检测的遗传学变异。方法对2019年1月至2022年8月于宁波市妇女儿童医院就诊并接受CMA检测的16p11.2综合征患者的临床指征、遗传学结果、家系调查及妊娠结局进行描述性分析。结果发现22例患者(20例胎儿、2例患儿)的16p11.2核心区域拷贝数变异,16p11.2综合征的整体检出率为0.226%。其中8例胎儿超声异常(2例脊椎发育异常、1例泌尿系统异常、3例颈部透明层增厚、2例肠道回声增强),3例无创DNA结果异常,4例血清学筛查高风险,4例高龄妊娠。22例中10例行亲本验证,其中新发突变7例,遗传自母亲2例,遗传自父亲1例。另有1例胎儿核型异常,验证后遗传自母亲。20例胎儿中,9例活产分娩,1例诊断为先天性心脏病,语言发育迟缓,其余生长发育未见异常。2例患儿携带缺失片段,临床表现为全面性强直阵挛发作,其中1例合并生长发育迟缓。结论16p11.2综合征患者的骨骼、心脏、神经、泌尿系统以及语言发育异常,临床表型呈异质性与多样性,产前诊断仍需积累大量临床数据。

Objective To investigate clinical symptoms and genetic variations of patients with 16p11.2 microdeletion/microduplication syndrome by using chromosomal microarray analysis(CMA)technology.Methods Clinical indications,genetic results,family investigation and pregnancy outcome of patients with 16p11.2 syndrome who received CMA testing in Ningbo Municipal Women and Children's Hospital from January 2019 to August 2022 were descriptively analyzed.Results 22 patients(20 fetuses,2 children)had copy number variation in core region of 16p11.2,and overall detection rate of 16p11.2 syndrome was 0.226%.Among them,there were 8 fetuses with ultrasonic abnormalities(2 cases of spinal dysplasia,1 case of urinary system abnormality,3 cases of thickened nuchal translucency(NT),2 cases of enhanced intestinal echos),3 cases had abnormal results of non-invasive prenatal testing(NIPT),4 cases were at high-risk of 16p11.2 syndrome by serological screening,and 4 cases had advanced(elderly)pregnancies.Of 22 patients,10 patients underwent parental verification,among which 7 cases were new mutations,2 cases were inherited from the mother and 1 case was inherited from the father.There was also one case of abnormal fetal karyotype,which was verified to be inherited from the mother.Among these 20 fetuses,9 fetuses were born live,1 fetus was diagnosed as congenital heart disease(CHD)and language retardation,and the rest had no abnormalities in growth and development.Two patients who carried missing fragments presented with generalized tonic-clonic seizures,one of which was accompanied by growth retardation.Conclusion Patients with 16p11.2 syndrome have abnormalities in bone,heart,nervous system,urinary system and language development,and their clinical phenotypes are heterogeneous and diverse,and a large amount of clinical data needs to be accumulated for prenatal diagnosis.