Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian patients.

Autor: Borsatto T; Post Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.; BRAIN Laboratory, Center for Experimental Research (CPE), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil., Sperb-Ludwig F; Post Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.; BRAIN Laboratory, Center for Experimental Research (CPE), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil., Lima SE; BRAIN Laboratory, Center for Experimental Research (CPE), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.; Centro Universitário Ritter dos Reis, Porto Alegre, RS, Brazil., S Carvalho MR; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., S Fonseca PA; Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., S Camelo J Jr; Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil., M Ribeiro E; Hospital Infantil Albert Sabin, Fortaleza, CE, Brazil., F V de Medeiros P; Universidade Federal de Campina Grande, Campina Grande, PB, Brazil., M Lourenço C; Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil., F M de Souza C; Medical Genetics Service, HCPA, Porto Alegre, RS, Brazil., Boy R; Departamento de Pediatria, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Félix TM; Medical Genetics Service, HCPA, Porto Alegre, RS, Brazil., M Bittar C; Post Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.; Medical Genetics Service, HCPA, Porto Alegre, RS, Brazil., L C Pinto L; Hospital Infantil Joana de Gusmão, Florianópolis, SC, Brazil., C Neto E; CTN Diagnósticos, Porto Alegre, RS, Brazil., J Blom H; Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, University Medical Centre Freiburg, Freiburg, Germany., D Schwartz IV; Post Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.; BRAIN Laboratory, Center for Experimental Research (CPE), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.; Medical Genetics Service, HCPA, Porto Alegre, RS, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2017 May 12; Vol. 12 (5), pp. e0177503. Date of Electronic Publication: 2017 May 12 (Print Publication: 2017).
DOI: 10.1371/journal.pone.0177503
Abstrakt: Introduction: The association between the BTD genotype and biochemical phenotype [profound biotinidase deficiency (BD), partial BD or heterozygous activity] is not always consistent. This study aimed to investigate the genotype-biochemical phenotype association in patients with low biotinidase activity.
Methods: All exons, the 5'UTR and the promoter of the BTD gene were sequenced in 72 Brazilian individuals who exhibited low biotinidase activity. For each patient, the expected biochemical phenotype based on the known genotype was compared with the observed biochemical phenotype. Additional non-genetic factors that could affect the biotinidase activity were also analysed.
Results: Most individuals were identified by neonatal screening (n = 66/72). When consecutive results for the same patient were compared, age, prematurity and neonatal jaundice appeared to affect the level of biotinidase activity. The biochemical phenotype at the time of the second blood collection changed in 11/22 patients compared to results from the first sample. Three novel variants were found: c.1337T>C (p.L446P), c.1466A>G (p.N489S) and c.962G>A (p.W321*). Some patients with the same genotype presented different biochemical phenotypes. The expected and observed biochemical phenotypes agreed in 68.5% of cases (concordant patients). The non-coding variants c.-183G>A, c.-315A>G and c.-514C>T were present in heterozygosis in 5/17 discordant patients. In addition, c.-183G>A and c.-514C>T were also present in 10/37 concordant patients.
Conclusions: The variants found in the promoter region do not appear to have a strong impact on biotinidase activity. Since there is a disparity between the BTD genotype and biochemical phenotype, and biotinidase activity may be affected by both genetic and non-genetic factors, we suggest that the diagnosis of BD should be based on more than one measurement of plasma biotinidase activity. DNA analysis can be of additional relevance to differentiate between partial BD and heterozygosity.
Databáze: MEDLINE
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