罕见的6p重复伴末端缺失综合征1例患儿的临床表型及遗传学分析

Clinical phenotype and genetic analysis of a rare case with 6p duplication and terminal deletion syndrome

目的探讨1例生长发育迟缓和智力低下(DD/ID)患儿的遗传学病因。方法选取2023年6月3日因"生长及智力发育迟缓、颅面部多发畸形、反复上呼吸道感染"就诊于深圳市龙华区妇幼保健院的1例女性DD/ID患儿及其父母作为研究对象。对患儿及其父母进行外周血染色体核型分析、低深度全基因组拷贝数变异测序(CNV-seq)和染色体微阵列分析(CMA),用荧光原位杂交(FISH)对候选拷贝数变异(CNV)进行家系验证。本研究通过深圳市龙华区妇幼保健院医学伦理委员会的审查(伦理号:2023052504)。结果患儿为8岁女性,具有不明原因的生长及智力发育落后、多发颅面部畸形、反复感染。患儿的外周血染色体G显带核型为46,XX,add(6)(q23),其父母核型未见异常。CNV-seq检测提示患儿6p25.3p22.3区存在21.38 Mb片段重复,6p25.3区存在0.78 Mb末端缺失。CMA检测证实患儿存在6p25.3(chr:934267_22310728)区段重复,6p25.3存在近端粒区(chr:156975_931936)缺失。FISH检测提示患儿的CNV为新发变异。结论联合外周血染色体G显带核型分析、CNV-seq、CMA及FISH检测确诊了1例DD/ID患儿的病因。患儿的异常表型可能是由6p重复伴末端缺失所致。

ObjectiveTo explore the genetic basis for a child with developmental delay and intellectual deficit(DD/ID).MethodsA child who was admitted to the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City on June 3,2023 due to DD/ID,craniofacial malformations,and recurrent infections of upper respiratory tract was selected as the study subject.G-banded chromosomal karyotyping was carried out for the child and her parents.Low-depth genome-wide copy number variation sequencing(CNV-seq)and chromosomal microarray analysis(CMA)were used to screen for genome-wide copy number variation(CNV),and fluorescence in situ hybridization(FISH)was used to verify the origin of candidate CNV.This study was approved by the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City(Ethics No.2023052504).ResultsThe child,an 8-year-old girl,had featured unexplained growth and intellectual development delay,multiple craniofacial malformations,and recurrent infections of the upper respiratory tract.She was found to have a karyotype of 46,XX,der(6)add(6)(q23),while both of her parents were normal.Both CNV-seq and CMA showed that the child has harbored a 21.38 Mb interstitial duplication at 6p25.3p22.3 and a 0.78 Mb terminal deletion at 6p25.FISH verified that both the duplication and deletion had occurred de novo.ConclusionThe abnormal phenotype of the child may be attributed to the 6p duplication and terminal deletion.