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Effect of BTD gene variants on in vitro biotinidase activity.
Borsatto, Taciane; Sperb-Ludwig, Fernanda; Blom, Henk J; Schwartz, Ida V D.
Afiliação
  • 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,. Electronic address: fsperb@gmail.co
  • Blom HJ; Metabolic Unit, Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC, Rotterdam, the Netherlands,. Electronic address: h.j.blom@erasmusmc.nl.
  • Schwartz IVD; 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, Por
Mol Genet Metab ; 127(4): 361-367, 2019 08.
Article em En | MEDLINE | ID: mdl-31337602
INTRODUCTION: Biotinidase deficiency (BD), an autosomal recessive disease, is classified into profound (activity <10%) or partial BD (activity 10-30%). The most frequent variant in patients worldwide is c.1330G > C (p.Asp444His), which is associated with partial BD. In vivo studies indicate that this variant reduces the biotinidase activity by 50%. The objective of this study was to evaluate the in vitro effect of p.Asp444His and of five novel variants identified among Brazilian individuals showing low activity of biotinidase in serum. METHODS: The variants c.119 T > C (p.Leu40Pro), c.479G > A (p.Cys160Tyr), c.664G > A (p.Asp222Asn), c.1330G > C (p.Asp444His), c.1337 T > C (p.Leu446Pro), c.1466A > G (p.Asn489Ser) and the wild type (wt) BTD gene were expressed in HEK 293 cells. Biotinidase activity was quantified by colorimetric method in cells homogenates and culture medium. The wtBTD activity was considered 100%. RESULTS: The p.Leu40Pro, p.Cys160Tyr and p.Leu446Pro variants were associated to impaired biotinidase activity (activity in cells: 33%, 14%, 0%, respectively; activity in medium: 7%, 0.3%, 2%, respectively) and undetectable amount of protein in intra and extracellular space. The p.Asn489Ser variant had these effects restricted to the extracellular space (activity in medium: 43%), and the p.Asp222Asn variant showed normal activity. The expression of p.Asp444His variant resulted in detectable protein and slightly reduced activity only in cells (activity in cells: 46%; activity in medium: 115%). CONCLUSION: Our findings suggest that the p.Leu40Pro, p.Cys160Tyr and p.Leu446Pro variants are deleterious; the p.Asn489Ser is probably related to a mild biochemical phenotype; and p.Asp222Asn variant is probably not deleterious. The p.Asp444His variant seems to code for a protein with variable activity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Deficiência de Biotinidase / Biotinidase Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Mol Genet Metab Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / METABOLISMO Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Deficiência de Biotinidase / Biotinidase Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Mol Genet Metab Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / METABOLISMO Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos