Work

The heterozygous c.2241G>C variation in FGFR2 may cause autosomal dominant Kirner’s deformity in a Chinese Han pedigree

Year: 2026

Type: article

Abstract: OBJECTIVE: Kirner’s deformity is a progressive deformity of the distal phalange of the little finger in a volar and radial direction. The FGFR2 gene plays a critical role in skeletal development and growth, with abnormal expression and activation of FGFR2 being associated with skeletal abnormalities. This study presents a family with Kirner’s deformity involving multiple patients. METHODS: Whole-exome sequencing was performed. SIFT, MutationTaster and Gerp+, while Clustal Omega was used for conservative analysis. In addition, I-TASSER was used to predict the 3D protein model. PyMOL was used for comparative analysis between abnormal and normal proteins. RESULTS: Sequencing data revealed that the proband, affected father, and son all carried a heterozygous missense variation c.2241G>C (p. Q747H) in FGFR2. Bioinformatic analysis suggested the potential pathogenicity of this variation. While the spatial structure of the protein variant was not significantly altered, the FGFR2 variation (p.Q747H) disrupted a hydrogen bond between Gln 747 and Ser 746, leading to significant changes in ligand and enzyme binding active sites. This structural alteration is predicted to impair binding to the Mg2+ ligand, thereby potentially disrupting downstream signaling pathways. This proposed mechanism provides a plausible explanation for the observed abnormal expression of bone development genes. CONCLUSION: These findings are consistent with a model in which the novel FGFR2 variant could impair protein function, a hypothesis that warrants further investigation. Our study identifies a new variant in the variational spectrum of Kirner’s deformity and expands the variational spectrum of the FGFR2 gene.

Source: BMC Medical Genomics

DOI: 10.1186/s12920-026-02312-x

Authors: Mingyi Ma, Hua Li, Xiaqing Wu, Kai Guo, Shaokun Chen, Songhua Zhao

Institutions: Southwest Medical University, Affiliated Hospital of Southwest Medical University

Language: English

Topic: Congenital limb and hand anomalies

Subfield: Developmental Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,190