A fetus with Neurodevelopmental disorders with deformed facial features and distal skeletal abnormalities due to a rare variant of ZMIZ1 gene and literature review.
10.3760/cma.j.cn511374-20251129-00693
- Author:
Jinghui ZOU
1
;
Haibo LI
;
Lulu YAN
Author Information
1. Central Laboratory for Birth Defects Prevention and Control, The Affiliated Women and Children's Hospital of Ningbo University, Ningbo, Zhejiang 315012, China. luluyan0228@sina.com.
- Publication Type:English Abstract
- MeSH:
Humans;
Female;
Pregnancy;
Neurodevelopmental Disorders/genetics*;
Transcription Factors/genetics*;
Fetus/abnormalities*;
Exome Sequencing;
Prenatal Diagnosis
- From:
Chinese Journal of Medical Genetics
2026;43(4):295-300
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the clinical manifestations and genetic etiology of a fetus with Neurodevelopmental disorders with deformed facial features and distal skeletal abnormalities (NEDDFSA).
METHODS:Clinical data of a NEDDFSA fetus diagnosed at the Affiliated Women and Children's Hospital Affiliated to Ningbo University in March 2025 was selected as the study subject. Whole-exome sequencing (WES) was carried out on the amniotic fluid and parental peripheral blood samples, and candidate variants was verified by Sanger sequencing. The pathogenicity of candidate variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094).
RESULTS:At 30 weeks of gestation, the fetus was found to have microcephaly, short femur and intrauterine growth restriction. WES revealed that the fetus harbored a de novo heterozygous frameshift variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene, which was rated as pathogenic (PM2_Supporting+PS2_Supporting+PVS1). Combined with 25 cases from the literature, the main manifestations of patients have included intellectual disability, growth retardation and cranio-limb skeletal dysplasia, albeit without clear genotype-phenotype correlation.
CONCLUSION:The de novo variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene probably underlay the NEDDFSA in this fetus. Genetic testing has enabled accurate prenatal diagnosis and provided evidence for genetic counseling and reproductive guidance of this family.
