18号环状染色体2例患儿的综合诊断与遗传学分析  

Comprehensive diagnosis and genetic analysis of two children with ring chromosome 18

作　　者：丁哲[1] 梅世月 章波 孔京慧 刘磊[1] 张振华[1] 王超杰[1] 张耀东 Ding Zhe;Mei Shiyue;Zhang Bo;Kong Jinghui;Liu Lei;Zhang Zhenhua;Wang Chaojie;Zhang Yaodong(Institute of Pediatric Medicine,Henan Provincial Key Laboratory of Children′s Genetics and Metabolic Diseases,Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou Children′s Hospital,Zhengzhou,Henan 450018,China)

机构地区：[1]郑州大学附属儿童医院(河南省儿童医院郑州儿童医院)儿科医学研究所,河南省儿童遗传代谢性疾病重点实验室,郑州450018

出　　处：《中华医学遗传学杂志》2024年第9期1110-1116,共7页Chinese Journal of Medical Genetics

摘　　要：目的明确2例18号环状染色体患儿的遗传学诊断,分析其变异的形成机制及表型特点。方法选取2022年6月和2023年3月于河南省儿童医院就诊的2例患儿为研究对象。应用拷贝数变异测序(CNV-seq)、G显带染色体核型分析及全外显子组测序(WES)技术对患儿进行检测。本研究通过河南省儿童医院医学伦理委员会的审查(伦理号:2023-K-075)。结果患儿1主要表现为发育迟滞、脑白质发育不良、1型糖尿病及小阴茎,染色体核型结果为46,XY,r(18)(p11.21q22.1)[40]/46,XY[7],CNV-seq检测结果显示其染色体18p11.21p11.32区缺失14.86 Mb,18q22.1q23区缺失14.02 Mb。患儿2主要表现为特殊面容、脑白质髓鞘化落后约1个月、发育迟滞、房间隔缺损、重度感音神经性耳聋、先天性喉喘鸣,染色体核型结果为46,XY,r(18)(p11.2q23),CNV-seq检测结果显示其染色体18p11.21p11.32区缺失14.86 Mb,18q21.32q23区缺失20.74 Mb。2例患儿WES检测均未发现明确的致病性单核苷酸变异位点,但提示18号染色体存在大片段缺失。结论2例患儿均被确诊为18号环状染色体综合征。2例患儿在18q区域缺失范围不同,18号环状染色体的嵌合比例也不同(患儿1为嵌合型,患儿2为非嵌合型),这可能是造成2例患儿表型差异的主要原因。2例患儿的1型糖尿病及小阴茎表型为18号环状染色体综合征新的临床表型。ObjectiveTo clarify the genetic diagnosis of two children with ring chromosome 18 and explore their mechanisms and clinical phenotypes.MethodsTwo patients treated at the Children′s Hospital of Henan Province respectively in June 2022 and March 2023 were selected as the study subjects.Genetic testing and diagnosis were carried out through copy number variation sequencing(CNV-seq),G-banded chromosomal karyotyping,and whole exome sequencing(WES).This study was approved by the Children′s Hospital of Henan Province(Ethics No.2023-K-075).ResultsChild 1 had mainly manifested developmental delay,white matter hypoplasia,type 1 diabetes mellitus,and micropenis.He was found to have a chromosomal karyotype of 46,XY,r(18)(p11.21q22.1)[40]/46,XY[7],and CNV-seq results showed that he has a 14.86 Mb deletion at 18p11.21p11.32 and a 14.02 Mb deletion at 18q22.1q23.Child 2 had peculiar facial features,delayed white matter myelination,developmental delay,atrial septal defect,severe sensorineural deafness,and congenital laryngeal stridor.He was found to have a chromosomal karyotype of 46,XY,r(18)(p11.2q23).CNV-seq result proved that he had a 14.86 Mb deletion at 18p11.21p11.32 and a 20.74 Mb deletion at 18q21.32q23.WES has failed to detect single nucleotide variants(SNVs)in either child,but revealed a large segmental deletion at chromosome 18 in both of them.ConclusionBoth children were diagnosed with ring chromosome 18 syndrome.The different size of the deletional fragments in the 18q region and mosaicism of ring chromosome 18 in child 1 may underlay the variation in their clinical phenotypes.The type 1 diabetes mellitus and micropenis noted in both children are novel features for ring chromosome 18 syndrome.

关 键 词：18号环状染色体综合征 18q缺失综合征 脑白质发育不良 1型糖尿病 拷贝数变异测序 

分 类 号：R725.9[医药卫生—儿科]