Case Report: Identification of a de novo Microdeletion 1q44 in a Patient With Seizures and Developmental Delay

Abstract

Objective: 1q44 microdeletion syndrome is difficult to diagnose due to the wide phenotypic spectrum and strong genetic heterogeneity. We explore the correlation between the chromosome microdeletions and phenotype in a child with 1q44 microdeletion syndrome, we collected the clinical features of the patient and combined them with adjacent copy number variation (CNV) regions previously reported. Methods: We collected the full medical history of the patient and summarized her clinical symptoms. Whole-exome sequencing (WES) and CapCNV analysis were performed with DNA extracted from both the patient's and her parents' peripheral blood samples. Fluorescent quantitative PCR (q-PCR) was performed for the use of verification to the CNV regions. Results: A 28.7 KB microdeletion was detected in the 1q44 region by whole-exome sequencing and low-depth whole-genome sequencing. The deleted region included the genes COX20 and HNRNPU. As verification, karyotype analysis showed no abnormality, and the results of qPCR were consistent with that of whole-exome sequencing and CapCNV analysis. Conclusion: The patient was diagnosed with 1q44 microdeletion syndrome with clinical and genetic analysis. Analyzing both whole-exome sequencing and CapCNV analysis can not only improve the diagnostic rate of clinically suspected syndromes that present with intellectual disability (ID) and multiple malformations but also support further study of the correlation between CNVs and clinical phenotypes. This study lays the foundation for the further study of the pathogenesis of complex diseases.

Keywords: 1q44 microdeletion syndrome; copy number variation; developmental delay; seizure; whole exon sequencing.

Figure 1

Female patient at the age of 5 years old presenting with facial dysmorphic signs including apparent asymmetry hypoplasia of eyes (A), widely spaced front teeth (B), Simian crease (C), and polydactyly (D).

Figure 2

MRI of the patient's brain showing dilation of bilateral ventricles, a small patchy abnormal signal in paraventricular white matter (A), hypogenesis of corpus callosum (B), small right eye, and abnormal shape and signal of the lens (C,D).

Figure 3

The chromosome microarray did not detect duplicates or microdeletions in the chromosome. This karyogram was generated by Genoglyphix v3.0 according to the microarray results. Triangle markers on the right side of the chromosomes indicate the alteration locus. Pink indicates duplication; blue indicates deletion, and gray indicates duplication or deletion excluded by Genoglyphix v3.0.

Figure 4

Results of CNV analysis based on exome trapping sequencing depth in the patient. It shows a 28.7 KB heterozygous deletion (chr1:244999016-245027609, hg19) in the 1q44 region. Overview of patient's chromosome 1 deletion and schematic diagram of the gene contained in the deletion region.

Figure 5

gDNA level validated by real-time fluorescent quantitative PCR in the 1q44 region. The results suggested that the patient had a heterozygous deletion in the COX20 (A) and HNRNPU (B) genes (relative quantification ratio close to 0.5). Additionally, the parents of the patient had no deletion in COX20 and HNRNPU, suggesting that this variant was a new variant. C1 and C2 stand for controls, P stands for patient, F stands for father, and M stands for mother. Differences were considered significant at p < 0.05. ****p < 0.0001.