Clinical phenotype and genetic analysis of a fetus with a novel mutation of OTX2 gene.
10.3760/cma.j.cn511374-20250217-00077
- Author:
Ying ZHOU
1
,
2
;
Yuxin ZHANG
;
Lulu YAN
;
Changshui CHEN
;
Haibo LI
Author Information
1. Central Laboratory of Birth Defects Prevention and Control, the Affiliated Women and Children's Hospital of Ningbo University, Ningbo, Zhejiang 315012, China. Lihaibo-775@
2. com.
- Publication Type:English Abstract
- MeSH:
Humans;
Otx Transcription Factors/genetics*;
Female;
Pregnancy;
Phenotype;
Microphthalmos/diagnostic imaging*;
Mutation;
Fetus/abnormalities*;
Male;
Adult;
Retrospective Studies;
Exome Sequencing
- From:
Chinese Journal of Medical Genetics
2025;42(8):1011-1015
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the clinical characteristics and genetic etiology of a fetus with bilateral ear malformation and microphthalmia.
METHODS:A fetus diagnosed with Syndromic Microphthalmia 5 (MCOPS5) on January 29, 2024 at Ningbo Women and Children's Hospital was selected as the study subject. A retrospective study was conducted to collect clinical data. Peripheral blood samples (3 mL) were collected from the parents, and amniotic fluid (10 mL) was obtained from the fetus. Genomic DNA was extracted and subjected to whole-exome sequencing (WES). Candidate variants were validated by Sanger sequencing of the family members. The pathogenicity of the candidate variant was classified according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Ningbo Women and Children's Hospital (Ethics No.: EC2023-094).
RESULTS:The gestational age of the fetus was 23+2 weeks. Prenatal magnetic resonance imaging (MRI) revealed hypoplastic left external ear, bilateral reduced eyeball volume, and abnormal brain parenchyma development. WES has identified a heterozygous frameshift variant in the OTX2 gene (NM_021728.4: c.706_725del, p.Thr236ProfsTer17). Sanger sequencing confirmed that neither parent has carried the same variant, indicating a de novo origin. According to the ACMG guidelines, this variant was classified as likely pathogenic (PVS1_Strong+PM2_Supporting+PS2_Supporting).
CONCLUSION:The heterozygous frameshift variant (NM_021728.4: c.706_725del) of the OTX2 gene probably underlay the pathogenesis of this fetus. Above finding has expanded the mutational spectrum of OTX2 gene and may contribute to the understanding of syndromic microphthalmia.
