Identification of a novel isolated 4q35.2 microdeletion in a Chinese pediatric patient using chromosomal microarray analysis: a case report and literature review

Abstract

Background Isolated terminal 4q35.2 microdeletion is an extremely rare copy number variant affecting people all over the world. To date, researchers still have controversial opinions and results on its pathogenicity. Here, we aim to present a Chinese pediatric patient with terminal 4q35.2 microdeletion and use this case to clarify the underlying genotype–phenotype correlation. Methods A 17-year-old boy from Quanzhou, South China, was recruited as the main subject in this study. Karyotype and single-nucleotide polymorphism (SNP) based microarray analysis were carried out to detect chromosomal abnormalities and copy number variants in this family. Trio whole exome sequencing (Trio-WES) was performed to investigate the potential pathogenic variant in this family. Results During observation, we identified abnormal clinical phenotypes including upper eyelid ptosis, motor developmental delay, abnormal posturing, abnormality of coordination, attention deficit hyperactivity disorder, and involuntary movements in the patient. SNP array analysis results confirmed a case of 2.0 Mb 4q35.2 microdeletion and parental SNP array verification results indicated that the terminal 4q35.2 microdeletion was inherited from his mother. No copy number variants were detected in his father. In addition, the trio-WES results demonstrated none of pathogenic or likely pathogenic variants in the patient. Conclusions This study brings a novel analysis of a case of 2.0 Mb terminal 4q35.2 microdeletion affecting a Chinese individual. In addition, additional clinical symptoms such as upper eyelid ptosis and involuntary movements were first reported to affect a patient with terminal 4q35.2 microdeletion, which may broaden the phenotype spectrum of the condition.

Optical Genome Mapping Identifies a Novel Unbalanced Translocation Between Chromosomes 4q and 6q Leading to Feeding Difficulties and Hypotonia in a Neonate: A Case Report

“…Additionally, some parents of patients with 4q35.2 microdeletions did not show abnormal clinical characteristics, which may reflect the characteristics of incomplete penetrance. 11 Although the neonatal patient in this study did not show signs of a neurodevelopmental disorder, his mother exhibited mild ID. Therefore, this cannot rule out the possibility of the proband having intellectual disabilities after birth or in childhood.…”

“…The most common manifestations include developmental delay and intellectual disability (ID); some patients also exhibit abnormal behavior and special facial features. [6][7][8][9][10][11][12][13][14][15][16][17] Due to the limited number of reported cases of these SVs and the corresponding phenotypic heterogeneity, there remains controversy regarding the pathogenicity of this variant.…”