First characterization of LTBP3 variants in two Moroccan families with hypoplastic amelogenesis imperfecta

Abstract

Objectives: To decipher and improve the molecular diagnosis of Hypoplastic Amelogenesis Imperfecta in Morocco.

Design: Using whole exome sequencing, we analyzed two Moroccan families with Hypoplastic Amelogenesis Imperfecta. The 2 patients from the first family had dental anomalies and short stature syndrome, brachyolmia and nephrocalcinosis with difference in severity, while the proband of the second family had Hypoplastic Amelogenesis Imperfecta with a suspicion of brachyolmia.

Results: We identified two novel LTBP3 homozygous variants, the c.2495delT deletion (p.Phe832SerfsTer36) and the c.3716 G>A (p.Cys1239Tyr) missense variant, respectively. Molecular modelling and stability analyses of the missense variant disclosed a possible destabilization of the wild-type structure.

Conclusion: Although LTBP3 variants were related to this phenotype in various populations, we report the first LTBP3 variants in the Moroccan population, in families with Hypoplastic Amelogenesis Imperfecta.

Keywords: Brachyolmia; DASS; Hypoplastic amelogenesis imperfecta; LTBP3; Moroccan population; Whole exome sequencing.