Neurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: A follow‐up study of four Chinese children carriers
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...
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doaj-76121a208b1f407eb15d10f188efa2a92020-11-25T04:09:41ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-11-01811n/an/a10.1002/mgg3.1485Neurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: A follow‐up study of four Chinese children carriersHua Xie0Fang Liu1Yu Zhang2Qian Chen3Shaofang Shangguan4Zhijie Gao5Nan Wu6Jian Wang7Xiaodai Cui8Lin Wang9Xiaoli Chen10Department of Medical Genetics Capital Institute of Pediatrics Beijing ChinaDepartment of Medical Genetics Capital Institute of Pediatrics Beijing ChinaDepartment of Laboratory Center Capital Institute of Pediatrics Beijing ChinaDepartment of Neurology Affiliated Children’s Hospital of Capital Institute of Pediatrics Beijing ChinaDepartment of Medical Genetics Capital Institute of Pediatrics Beijing ChinaDepartment of Neurology Affiliated Children’s Hospital of Capital Institute of Pediatrics Beijing ChinaDepartment of Orthopedic Surgery Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences Beijing ChinaShanghai Children’s Medical Center Shanghai Jiaotong University School of Medicine Shanghai ChinaDepartment of Laboratory Center Capital Institute of Pediatrics Beijing ChinaDepartment of Preventive Health Care Affiliated Children’s Hospital of Capital Institute of Pediatrics Beijing ChinaDepartment of Medical Genetics Capital Institute of Pediatrics Beijing ChinaAbstract 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.https://doi.org/10.1002/mgg3.148516p11.2 microdeletionfrequencyneurodevelopmental disorderneurodevelopmental trajectorywhole‐genome expression profiling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hua Xie Fang Liu Yu Zhang Qian Chen Shaofang Shangguan Zhijie Gao Nan Wu Jian Wang Xiaodai Cui Lin Wang Xiaoli Chen |
spellingShingle |
Hua Xie Fang Liu Yu Zhang Qian Chen Shaofang Shangguan Zhijie Gao Nan Wu Jian Wang Xiaodai Cui Lin Wang Xiaoli Chen Neurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: A follow‐up study of four Chinese children carriers Molecular Genetics & Genomic Medicine 16p11.2 microdeletion frequency neurodevelopmental disorder neurodevelopmental trajectory whole‐genome expression profiling |
author_facet |
Hua Xie Fang Liu Yu Zhang Qian Chen Shaofang Shangguan Zhijie Gao Nan Wu Jian Wang Xiaodai Cui Lin Wang Xiaoli Chen |
author_sort |
Hua Xie |
title |
Neurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: A follow‐up study of four Chinese children carriers |
title_short |
Neurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: A follow‐up study of four Chinese children carriers |
title_full |
Neurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: A follow‐up study of four Chinese children carriers |
title_fullStr |
Neurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: A follow‐up study of four Chinese children carriers |
title_full_unstemmed |
Neurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: A follow‐up study of four Chinese children carriers |
title_sort |
neurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: a follow‐up study of four chinese children carriers |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2020-11-01 |
description |
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. |
topic |
16p11.2 microdeletion frequency neurodevelopmental disorder neurodevelopmental trajectory whole‐genome expression profiling |
url |
https://doi.org/10.1002/mgg3.1485 |
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