Association analysis of HOXA1 and FOXF2 gene variants with genetic susceptibility in a multigenerational family with exotropia
10.3980/j.issn.1672-5123.2025.10.25
- VernacularTitle:外斜视多代家系中HOXA1和FOXF2基因变异与遗传易感性的关联分析
- Author:
Yaxin HU
1
,
2
;
Hongyan DU
1
,
2
Author Information
1. Inner Mongolia Medical University, Hohhot 010050, Inner Mongolia Autonoumous Region, China
2. Department of Ophthalmology, Inner Mongolia People's Hospital, Hohhot 010017, Inner Mongolia Autonoumous Region, China
- Publication Type:Journal Article
- Keywords:
exotropia;
HOXA1 gene;
FOXF2 gene;
gene variant;
association analysis;
genetic susceptibility
- From:
International Eye Science
2025;25(10):1688-1693
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the association between HOXA1 and FOXF2 gene variants and genetic susceptibility in multigenerational families with exotropia, and to elucidate the molecular genetic etiological mechanisms of exotropia.METHODS:A total of 10 multigenerational families with a definitive history of exotropia were recruited from September 2023 to February 2025, comprising 165 members(87 exotropia patients and 78 normal controls). Detailed ophthalmological examinations were performed, family pedigrees were constructed, peripheral blood samples were collected, genomic DNA was extracted, and PCR amplification followed by Sanger sequencing were used to detect exons and flanking sequences of the HOXA1 and FOXF2 genes. Identified variants were subjected to pathogenicity classification and association analyses.RESULTS:Among the 10 families, 5 variant sites in HOXA1(c.218G>A, c.385C>T, c.496A>G, c.652T>C, c.874C>T)and 4 in FOXF2(c.102C>T, c.344G>A, c.576T>C, c.892A>G)were identified. The HOXA1 c.496A>G variant showed statistically significant differences between carrier and noncarrier in exotropia angle, exotropia type, stereoscopic vision, and parallax(all P<0.05). The age of onset of FOXF2 gene c.344G>A mutation carrier group was younger than that of the non-carrier group(t=3.55, P=0.004).CONCLUSION:HOXA1 and FOXF2 gene variants are significantly associated with genetic susceptibility to exotropia, particularly influencing age of onset and deviation angle, offering novel targets for molecular diagnosis and precision treatment of exotropia.
