Novel Maternal Duplication of 6p22.3-p25.3 with Subtelomeric 6p25.3 Deletion: New Clinical Findings and Genotype-phenotype Correlations

Overview

Journal Mol Cytogenet

Publisher Biomed Central

Specialty Biochemistry

Date 2023 Jun 11

PMID 37303060

Authors

Liyu Zhang

Xiaoling Tie

Fengyu Che

Guoxia Wang

Ying Ge

Benchang Li

Ying Yang

Affiliations

Soon will be listed here.

Abstract

Background: Copy-number variants (CNVs) drive many neurodevelopmental-related disorders. Although many neurodevelopmental-related CNVs can give rise to widespread phenotypes, it is necessary to identify the major genes contributing to phenotypic presentation. Copy-number variations in chromosome 6, such as independent 6p deletion and 6p duplication, have been reported in several live-born infants and present widespread abnormalities such as intellectual disability, growth deficiency, developmental delay, and multiple dysmorphic facial features. However, a contiguous deletion and duplication in chromosome 6p regions have been reported in only a few cases.

Case Presentation: In this study, we reported the first duplication of chromosome band 6p25.3-p22.3 with deletion of 6p25.3 in a pedigree. This is the first case reported involving CNVs in these chromosomal regions. In this pedigree, we reported a 1-year-old boy with maternal 6p25-pter duplication characterized by chromosome karyotype. Further analysis using CNV-seq revealed a 20.88-Mb duplication at 6p25.3-p22.3 associated with a contiguous 0.66-Mb 6p25.3 deletion. Whole exome sequencing confirmed the deletion/duplication and identified no pathogenic or likely pathogenic variants related with the patient´s phenotype. The proband presented abnormal growth, developmental delay, skeletal dysplasia, hearing loss, and dysmorphic facial features. Additionally, he presented recurrent infection after birth. CNV-seq using the proband´s parental samples showed that the deletion/duplication was inherited from the proband´s mother, who exhibited a similar phenotype to the proband. When compared with other cases, this proband and his mother presented a new clinical finding: forearm bone dysplasia. The major candidate genes contributing to recurrent infection, eye development, hearing loss features, neurodevelopmental development, and congenital bone dysplasia were further discussed.

Conclusions: Our results showed a new clinical finding of a contiguous deletion and duplication in chromosome 6p regions and suggested candidate genes associated with phenotypic features, such as FOXC1, SERPINB6, NRN1, TUBB2A, IRF4, and RIPK1.

Citing Articles

The known structural variations in hearing loss and their diagnostic approaches: a comprehensive review.

Naghinejad M, Parvizpour S, Shekari Khaniani M, Mehri M, Mansoori Derakhshan S, Amirfiroozy A Mol Biol Rep. 2025; 52(1):131.

PMID: 39821465 DOI: 10.1007/s11033-025-10231-w.

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