RT info:eu-repo/semantics/article
T1 Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian patients
A1 Borsatto, Taciane
A1 Sperb-Ludwig, Fernanda
A1 Lima, Samyra E.
A1 Carvalho, María R.S.
A1 De Souza Fonseca, Pablo Augusto
A1 Camelo, José S.
A1 Ribeiro, Erlane M.
A1 De Medeiros, Paula F. V.
A1 Lourenço, Charles M.
A1 De Souza, Carolina F. M.
A1 Boy, Raquel
A1 Félix, Têmis M.
A1 Bittar, Camila M.
A1 Pinto, Louise L. C.
A1 Neto, Eurico C.
A1 Blom, Henk J.
A1 Schwartz, Ida V. D.
A2 Producción Animal
K1 Genética
K1 Biotinidase
K1 Genotyping
K1 Mutations
K1 Human
K1 32 Ciencias Médicas
K1 2409 Genética
AB [EN] 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. 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. 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.
PB Plos
LK https://hdl.handle.net/10612/17935
UL https://hdl.handle.net/10612/17935
NO Borsatto, T., Sperb-Ludwig, F., Lima, S. E., Carvalho, M. R. S., Fonseca, P. A. S., Camelo, J. S., Ribeiro, E. M., De Medeiros, P. F. V., Lourenço, C. M., De Souza, C. F. M., Boy, R., Félix, T. M., Bittar, C. M., Pinto, L. L. C., Neto, E. C., Blom, H. J., & Schwartz, I. V. D. (2017). Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian patients. PLoS ONE, 12(5). https://doi.org/10.1371/JOURNAL.PONE.0177503
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 21-may-2024