BTD Gene Mutations in Biotinidase Deficiency: Genotype-Phenotype Correlation.

Abstract

OBJECTIVE\nTo identify the biotinidase (BTD) gene mutations in patients with biotinidase deficiency in our region; and to determine the phenotype-genotype correlations in the presence of clinical findings.\n\n\nSTUDY DESIGN\nDescriptive study.\n\n\nPLACE AND DURATION OF STUDY\nDepartment of Medical Genetics and Pediatric Metabolism Outpatient Clinic, Faculty of Medicine, Harran University, between January 2018 and June 2020.\n\n\nMETHODOLOGY\nTwo hundred and nine patients, who were found positive for biotinidase deficiency in heel blood screening, were included. Genomic DNA was isolated from peripheral blood. Next-generation DNA sequencing analysis was performed using primers covering the exon regions of the BTD gene. The results were analysed by the mutation surveyor programme.\n\n\nRESULTS\nThe most common mutation was c.1330 G>C (p.D444H) and the second most common mutation was c.470 G>A (p.R157H). The majority of the mutations are missense; and they are especially located in the exon 4. The most frequent mutations were found to be D444H and R157H with a rate of 66.66% in symptomatic patients.\n\n\nCONCLUSION\nCommon mutations in BTD deficiencies were indentified. Associating them with phenotype-genotype data will assist clinicians in better genetic counselling and management in the future by implementing prevention programmes. Key Words: Biotinidase deficiency, BTD gene, Newborn screening, Inherited metabolic disease, Newborn screening programme.