Genetic analysis and prenatal diagnosis of structural brain abnormalities associated with TUBB gene c.155A>G variant.
10.3760/cma.j.cn511374-20250801-00472
- Author:
Yifan LIU
1
;
Wei SONG
;
Xinlian WANG
;
Yan RUAN
;
Meng ZHANG
;
Yujiao CHEN
;
Yan LIU
;
Puqing ZHANG
;
Li WANG
;
Yousheng YAN
Author Information
1. Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China. yys_521@ccmu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Humans;
Female;
Pregnancy;
Prenatal Diagnosis;
Tubulin/genetics*;
Adult;
Brain/diagnostic imaging*;
Male;
Pedigree;
DNA Copy Number Variations/genetics*;
Exome Sequencing;
Genetic Association Studies;
Magnetic Resonance Imaging
- From:
Chinese Journal of Medical Genetics
2026;43(2):136-142
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene.
METHODS:A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01).
RESULTS:Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3).
CONCLUSION:The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
