Identification of a rare missense variant in the gene SPATA31H1 associated with hereditary gingival fibromatosis in a large Chinese family

BACKGROUND: Hereditary gingival fibromatosis (HGF), a benign hereditary oral disease, is characterized by significant gingival hyperplasia. The disease typically manifests as autosomal dominant inheritance, with great genetic heterogeneity. In this study, we studied a four-generation Chinese kindred with nonsyndromic HGF, including 19 patients. Given the significant genetic heterogeneity of HGF, identifying novel pathogenic genes is crucial for advancing our understanding of the disease. This study offers a novel theoretical foundation for HGF research. METHODS: Family members underwent clinical examination and data collection. Pathogenic genes and mutation sites were identified using Whole Exome Sequencing (WES), SNP chip whole-genome linkage analysis, and Sanger sequencing. The impact of mutations on gene function was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blot and subcellular localization experiments. The potential pathogenic mechanism of HGF was explored through transcriptome sequencing of affected gingival tissues. RESULTS: Exome sequencing identified a novel heterozygous missense variant (c.14366G > T) in SPATA31H1 gene of the patient, resulting in a Tryptophan to Leucine substitution at the conserved amino acid position 4789 of the protein. Protein structure prediction, RT-qPCR, and western blotting analysis revealed that the missense variant in this gene was likely pathogenic. Transcriptome sequencing analysis of the family samples suggested that the variant affected pathways related to gingival fibrosis. CONCLUSIONS: In this study, it was found that a missense mutation in the gene SPATA31H1 is closely associated with non-syndromic HGF disease.