Data for: "Intra-familial phenotype variation in hypoplastic amelogenesis imperfecta under a complex genetic component: a family report, whole-exome sequencing, and literature review"

Supplementary material of exome analysis of the individuals investigated in this study. Introduction: Amelogenesis imperfecta (AI) refers to a group of conditions characterized by abnormalities in the development or function of the tooth enamel. Clinical manifestations include different forms and grades of enamel frailty, associated with sensitivity, tooth fractures, stains, abnormal dental form, absent teeth, etc. AI is genetically heterogeneous and over 70 genes have already been associated with autosomal dominant and recessive, X-linked, and oligogenic inheritance. Objective: to search for genetic variants in an AI family. Methodology: Here, we describe the clinical findings of an AI family, composed of five persons, four affected (the father and three daughters) and the unaffected mother. AI segregation pattern suggests dominant, X-linked inheritance. Genetic variants were screened using Whole Exome Sequencing. Results: The initial bioinformatic analysis was conducted in Qiagen QCI and the variant selection criteria used were to be present in the four affected family members and absent in the unaffected mother. Search terms used were “amelogenesis imperfecta”, tooth, and enamel. Several software were used to classify variants according to pathogenicity. Candidate variants emerged in six genes. Three of these variants were detected in autosomal genes: NM_031889.3(ENAM):c.1726T>C (p.F576L), NM_022168.4(IFIH1):c.1764dupA, (p.A589fs*21), and NM_032383.5(HPS3):c.1897A>T (p.M633L). Three variants were detected in X-linked genes: NM_006150.5(PRICKLE3):c.8C>G (p.A3G), NM_004484.4(GPC3):c.584A>G (p.N195S), and NM_152787.5(TAB3):c.1936G>A (p.V646M). None of these variants were classified as definitely likely pathogenic/pathogenic in AI. Discussion: Of these genes, only ENAM has been associated with AI previously, but IFIH1, PRICKLE3, and GPC3 are associated with dental/enamel development. The relatively large number of candidate genes/genetic variants detected may reflect an oligogenic component already proposed for AI. Conclusions: this study provides a set of new candidate genes and genetic variants for AI. Despite sharing the variants, AI-affected persons in this family show great phenotypic variation, suggesting the contribution of non-shared genetic or environmental components. (2025-06-08) To share raw data on clinical descriptions, literature review of ENAM-related phenotypes, exome results (SNVs and CNV). (2025-07-22)