Truncated Variants in FAM20A and WDR72 Genes Underlie Autosomal Recessive Amelogenesis Imperfecta in Four Pakistani Families

• DOI: 10.1007/s10528-025-11087-2
• Publication Date: 2025-03-19T20:41:07Z
• Authors: Sadaqat Ullah; Sher Alam Khan; Samin Jan; Salah Ud Din; Nazif Muhammad; Zia Ur Rehman; Abid Jan; Muhammad Tariq; Noor Muhammad; Abdul Ghani; Naveed Wasif; Saadullah Khan
• Keywords: Amelogenesis imperfecta; Sanger sequencing; Human genetics; Nonsense

Abstract Amelogenesis Imperfecta (AI) is a set of hereditary diseases affecting enamel development, leading to various types defects, potentially impacting oral health unassociated with other generalized defects. AI manifests in syndromic and non-syndromic forms can be inherited through autosomal recessive, dominant, or X-linked inheritance patterns. Genetic studies have identified sequence variants number genes (≥ 70) linked both AI, highlighting the genetic diversity underlying condition. The current study involved clinical evaluation exome sequencing, aimed at identifying causative four unrelated consanguineous Pakistani families presenting phenotypes. sequencing results revealed novel homozygous frameshift variant FAM20A : NM_017565.4, c.188dupA; p.(Asp63Glufs*17) A, B, C while nonsense WDR72 NM_182758.4, c.2686C > T; p. (Arg896*) family D. segregation was confirmed by Sanger sequencing. Bioinformatics analysis predicted pathogenicity these variants. These alterations suggest functional consequences, impairing proteins causing dental anomalies. This investigation significantly broadens our understanding ’s involvement AI. Furthermore, this highlights heterogeneity (involving study) within population.