Open AccessNeurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: A follow‐up study of four Chinese children carriers
Author(s) -
Xie Hua,
Liu Fang,
Zhang Yu,
Chen Qian,
Shangguan Shaofang,
Gao Zhijie,
Wu Nan,
Wang Jian,
Cui Xiaodai,
Wang Lin,
Chen Xiaoli
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1485
Subject(s) - microdeletion syndrome , intellectual disability , copy number variation , cohort , neurodevelopmental disorder , medicine , phenotype , genetics , pediatrics , gene , biology , genome , pathology
Abstract Background Neurodevelopmental disorders (NDDs) are a group of disorders with high genetic and phenotypic heterogeneities. The 16p11.2 microdeletion has been implicated as an important genetic risk factor for NDDs. Methods Multiple genetic tests were used to detect the 16p11.2 microdeletion from 918 Chinese children with NDDs. Targeted sequencing of genes in the 16p11.2 interval was performed in all carriers of the 16p11.2 microdeletion, and whole‐genome expression profiling analysis was performed for the patient carriers and normal carriers in their intra‐family. Results Three patients carrying the 16p11.2 microdeletion were screened out, indicating a frequency of 0.33% for the 16p11.2 microdeletion in this cohort. We reviewed the neurodevelopmental trajectories of the 16p11.2 microdeletion carriers from childhood to puberty and confirmed that this microdeletion was associated with abnormal neurodevelopment, with varied neurodevelopmental phenotypes. A differential PRRT2 genotype (rs10204, T>C) was identified between patients and normal carriers of the 16p11.2 microdeletion. Moreover, the determination of differential whole‐genome expression profiling demonstrated the destruction of the top‐ranked network in neurogenesis and accounted for observation of abnormal neurodevelopmental phenotypes in the 16p11.2 microdeletion carriers. Conclusions We have provided the frequency of the 16p11.2 microdeletion in a Chinese pediatric NDD cohort with a variable NDD phenotype from childhood to puberty, which is useful for Chinese geneticists/pediatricians to conduct the 16p11.2 microdeletion testing in children with NDDs.