Neurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: A follow-up study of four Chinese children carriers.
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.
['Xie|Hua|H|0000-0002-0069-3877', 'Liu|Fang|F|', 'Zhang|Yu|Y|', 'Chen|Qian|Q|0000-0001-9566-9003', 'Shangguan|Shaofang|S|', 'Gao|Zhijie|Z|', 'Wu|Nan|N|', 'Wang|Jian|J|0000-0003-3391-5250', 'Cui|Xiaodai|X|', 'Wang|Lin|L|', 'Chen|Xiaoli|X|0000-0003-0536-1553']
D000293:Adolescent D001321:Autistic Disorder D002648:Child D002872:Chromosome Deletion D025063:Chromosome Disorders D002885:Chromosomes, Human, Pair 16 D005260:Female D060045:Genes, Modifier D006579:Heterozygote D006801:Humans D007223:Infant D008607:Intellectual Disability D008297:Male D008565:Membrane Proteins D009154:Mutation D009419:Nerve Tissue Proteins D010641:Phenotype
neurodevelopmental trajectory 16p11.2 microdeletion neurodevelopmental disorder whole-genome expression profiling frequency