Further evidence of genetic heterogeneity segregating with hereditary gingival fibromatosis

Abstract

To clinically characterize and map the disease-associated locus in a five-generation Chinese family with autosomal dominant early-onset hereditary gingival fibromatosis (HGF). A complete oral examination was conducted. Genomic DNA samples were obtained from 14 individuals. Short tandem repeats markers, which encompass four previously known loci related to HGF, were genotyped. Two-point log of the odds (LOD) scores were calculated using MLINK program of the LINKAGE software, multipoint and non-parametric linkage (NPL) analysis were performed using the GENEHUNTER software. Clinical evaluation and histological examination of this family suggested typical features of HGF. The onset age was early in the generations, ranging between 1 and 2 years. None of the tested markers showed cosegregation among affected individuals. Genotyping data from four putative regions yielded significant negative two-point LOD scores (<-2.0) at theta=0. The maximum multipoint LOD scores and NPL analysis revealed exclusion of these loci as well. Exclusion of linkage in this family to any of the known HGF loci proved the existence of a novel locus for autosomal dominant HGF and showed that this rare disorder is far more heterogeneous than previously expected.