Genotype-Phenotype Analysis of 8q24.3 Duplication and 21q22.3 Deletion in a Chinese Patient and Literature Review

Abstract

<b><i>Introduction:</i></b> Copy number variants (CNVs) are responsible for many patients with short stature of unknown etiology. This study aims to analyze clinical phenotypes and identify pathogenic CNVs in a patient with short stature, intellectual disability, craniofacial deformities, and anal imperforation. <b><i>Methods:</i></b> G-banded karyotyping and chromosomal microarray analysis (CMA) was used on the patient to identify pathogenic causes. Fluorescence in situ hybridization (FISH) was applied to explore the abnormal genetic origin. Literatures were searched using identified CNVs as keywords in the PubMed database to perform genotype-phenotype analysis. <b><i>Results:</i></b> Cytogenetic analysis revealed a normal karyotype 46,XY. CMA detected a 6.1 Mb duplication at 8q24.3 and a 3.6 Mb deletion at 21q22.3. FISH confirmed that the abnormal chromosomes were inherited from paternal balanced translocation. We compared phenotypes of our patient with 6 patients with 8q24.3 duplication and 7 cases with 21q22.3 deletion respectively. <b><i>Conclusions:</i></b> A novel 8q24.3 duplication and 21q22.3 deletion was identified in a Chinese patient. Genotype-phenotype analysis demonstrated that patients with 8q24.3 duplication and 21q22.3 deletion had specific facial features, intellectual disability, short stature, and multiple malformations.