ENAMEL RENAL SYNDROME: A NOVEL HOMOZYGOUS FAM20A FOUNDER MUTATION IN 5 NEW BRAZILIAN FAMILIES

Objective To investigate mutations in FAM20A of 11 unreported patients with ERS from 5 different Brazilian families. Study Design Clinical examination, imaging, renal ultrasonography, laboratory tests and DNA sequencing were performed in 11 patients with ERS. Results The patients' ages ranged from 6 to 25 years old, and the presence of hypoplastic amelogenesis imperfecta, microdontia, spaced teeth, intrapulpal calcification, impacted posterior teeth with hyperplastic pericoronal follicle, gingival fibromatosis, ectopic calcifications on gingival and pericoronal tissues, and nephrocalcinosis were common findings to all patients. Only 4 patients showed abnormal results in laboratory tests (vitamin D, parathyroid hormone, phosphate, calcium). Intellectual disability and renal cysts were present in 2 patients each. Biallelic loss of function mutations in FAM20A gene, characterized by 1 base pair deletion in exon 11 (c.1447 delG) and resulting in a premature stop codon at p.GLU483 LYSfsX24 were detected in all patients strongly suggesting a founder effect. Conclusions Our results reinforce the distinct orofacial features of ERS, which are the clue for kidney examination and genetic testing. Here we report the largest series of patients with ERS of the same population, and describe, for the first time, a founder mutation for FAM20A gene. FAPEMIG, FAPESP, CAPES.