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Biotinidase deficiency : clinical and genetic studies of 38 Brazilian patients

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Biotinidase deficiency : clinical and genetic studies of 38 Brazilian patients

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Título Biotinidase deficiency : clinical and genetic studies of 38 Brazilian patients
Autor Borsatto, Taciane
Ludwig, Fernanda Sperb
Pinto, Louise Lapagesse de Camargo
Luca, Gisele Rozone de
Carvalho, Francisca Ligia Cirilo
Souza, Carolina Fischinger Moura de
Medeiros, Paula Frassinetti Vasconcelos de
Lourenço, Charles Marques
Omena Filho, Reinaldo Luna de
Camargo Neto, Eurico
Bernardi, Pricila
Leistner-Segal, Sandra
Schwartz, Ida Vanessa Doederlein
Abstract Background: Biotinidase deficiency (BD) is an inborn error of metabolism in which some genetic variants correlate with the level of enzyme activity. Biotinidase activity, however, may be artifactually low due to enzyme lability, premature birth, and jaundice; this hinders both phenotypic classification and the decision to implement therapy. This study sought to characterize the clinical and genetic profile of a sample of Brazilian patients exhibiting reduced biotinidase activity. Methods: This observational, multicenter study used a convenience sampling strategy, with sequencing of exons 2, 3, and 4 of the BTD gene. Results: The sample comprised 38 individuals with biochemical phenotypes defined a priori on the basis of biotinidase activity in serum/plasma (2 with profound deficiency, 9 with partial deficiency, 15 heterozygous, 1 borderline between partial deficiency and heterozygosity, 2 borderline between heterozygous and normal) or dried blood spot sample (n = 9, all with unspecified deficiency). Most patients were from Southern Brazil (n = 29/38) and were identified by neonatal screening (n = 33/38). Parental consanguinity was reported in two cases. The most commonly found genetic variants were c.1330G > C (p.D444H), c.755A > G (p.D252G), and c.[511G > A;1330G > C] (p.[A171T;D444H]), with allele frequencies of 50%, 9.4%, and 5.4% respectively. Three novel pathogenic variants were identified (c.119 T > C or p.L40P, c.479G > A or p.C160Y, and c.664G > A or p.D222N). Twenty-nine patients had two pathogenic variants detected (with cis/trans status ascertained in 26/29), six had only one variant, and three had no pathogenic variants detected. Genotyping confirmed the original phenotypic classification based on enzyme activity in 16/26 cases. Three polymorphic variants were identified in control individuals, of which two were nonpathogenic (c.1171C > T or p.P391S and c.1413 T > C or p.C471C, with a frequency of 1.5% and 5.5% respectively) and one pathogenic (c.1330G > C, frequency 4%). Conclusions: Our findings suggest that partial BD is the most common form of BD in Brazil, and expand current knowledge on the allelic heterogeneity of this condition.
Contido em BMC medical genetics. London. Vol. 15 (Sep. 2014), 7p.
Assunto Biotinidase
Genética
Triagem neonatal
[en] Brazil
[en] Genetic variants
[en] Low biotinidase
[en] Neonatal screening
Origem Estrangeiro
Tipo Artigo de periódico
URI http://hdl.handle.net/10183/111842
Arquivos Descrição Formato
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