目的:明确2例18号环状染色体儿童的基因诊断,探讨其机制和临床表型。
方法:选择分别于2022年6月和2023年3月在河南省儿童医院就诊的2例患者作为研究对象。通过拷贝数变异测序(CNV-seq)进行基因检测和诊断,G-带染色体核型分析,和全外显子组测序(WES)。
结果:儿童1主要表现为发育迟缓,白质发育不全,1型糖尿病,和微阴茎。他的染色体核型为46,XY,r(18)(p11.21q22.1)[40]/46,XY[7],CNV-seq结果显示,他在18p11.21p11.32处具有14.86Mb的缺失,在18q22.1q23处具有14.02Mb的缺失。2号孩子有奇特的面部特征,白质髓鞘形成延迟,发育迟缓,房间隔缺损,严重的感觉神经性耳聋,先天性喉鸣.他的染色体核型为46,XY,r(18)(第11.2季度)。CNV-seq结果证明他在18p11-21p11.32处有14.86Mb缺失,在18q21.32q23处有20.74Mb缺失。WES未能检测到任何一个孩子的单核苷酸变异(SNV),但在他们俩的18号染色体上发现了一个大的片段缺失。
结论:两个孩子都被诊断为18号环状染色体综合征。儿童1的18q区域中缺失片段的大小不同以及环染色体18的镶嵌性可能是其临床表型变异的基础。在两个孩子中注意到的1型糖尿病和微阴茎是18号环状染色体综合征的新特征。
OBJECTIVE: To clarify the genetic diagnosis of two children with ring chromosome 18 and explore their mechanisms and clinical phenotypes.
METHODS: Two 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).
RESULTS: Child 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.
CONCLUSIONS: Both 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.