30 de setembro de 2024 (segunda-feira) – 10h30min<\/p>\n
SEMIN\u00c1RIO DE QUALIFICA\u00c7\u00c3O (Doutorado)<\/strong><\/p>\n <\/p>\n D\u00c9VORA NATALIA RANDON<\/strong><\/p>\n Genetic Profile and Genotype-Phenotype Association for Biotinidase Deficiency in Brazil<\/strong><\/p>\n Orientadora: Dra. Ida Vanessa Doederlein Schwartz<\/p>\n Coorientadora: Dra. Fernanda Sperb-Ludwig<\/p>\n Banca Examinadora: Dra. Kristiane Michelin Tirelli e Dr. Fabiano de Oliveira Poswar<\/p>\n 30 de setembro de 2024 (segunda-feira)<\/p>\n 10h30min <\/strong><\/p>\n Presencial:\u00a0<\/strong>Anfiteatro do\u00a0Departamento\u00a0de\u00a0Gen\u00e9tica da UFRGS (Campus do Vale, pr\u00e9dio 43312)<\/p>\n <\/p>\n <\/p>\n Abstract<\/strong><\/p>\n Introduction:<\/strong> Biotinidase deficiency (BD) is an autosomal recessive disorder caused by pathogenic variants in the BTD<\/em> gene. This gene encodes the enzyme biotinidase (BTD), which is essential for the absorption of biotin, that acts as a cofactor for several carboxylase enzymes. BD is characterized by dermatological and neurological symptoms that can lead to severe clinical manifestations, and even death if not treated through oral biotin supplementation. Since 2012, Brazil has included BD in its National Newborn Screening Program, with diagnosis confirmed through enzymatic activity tests in plasma or serum. BD is classified as total (activity <10%) or partial (10-30%). However, biochemical classification can be inconclusive due to factors like prematurity or sample transportation. Genetic analysis arises as an important complement to clinical management. Over 250 pathogenic variants have been identified in the BTD<\/em> gene. The variant p.(Asp444His) is the most prevalent one, and it is associated with partial BD. This variant is also found in the pathogenic complex allele p.[(Ala171Thr);(Asp444His)], also frequent. The low prevalence of total BD and uncertainty regarding the need to treat partial BD raise concerns about the neonatal screening protocol and relevance. General Objective: <\/strong>This thesis aims to evaluate the genetic profile of BD and its relationship with phenotype in Brazilian individuals. Methods –<\/strong> Chapter 1:<\/strong> Multicentric observational study. Data from 54 Brazilian individuals with reduced BTD activity were added to those previously analyzed by our group (Borsatto et al., 2014; 2017), bringing the total to 126 participants. Whole blood or buccal mucosa samples were collected, along with data on enzymatic activity, prematurity, age, and symptoms. Based on enzymatic tests, participants were classified as total BD, partial BD, heterozygote, borderline, or normal. Genetic analysis of the BTD<\/em> gene was performed via Sanger sequencing, and novel variants were classified following the criteria of the American College of Medical Genetics and Genomics (ACMG). Chapter 2:<\/strong> A case report of a patient diagnosed at three years old with total BD, harboring a known pathogenic variant and suspected intronic variant not previously reported in the literature. Genetic analysis will be performed using next-generation sequencing. Chapter 3:<\/strong> A cross-sectional study of 1,000 healthy individuals from Rio Grande do Sul, with analysis of the p.(Asp444His) variant through TaqMan genotyping and Sanger sequencing of exon 4 of the BTD<\/em> gene to identify the composite allele p.[(Ala171Thr);(Asp444His)]. Results:<\/strong> Chapter 1:<\/strong> Based on enzymatic activity, 7 individuals were classified as having total BD, 25 as partial BD, 60 as heterozygotes, 11 as borderline, and 7 as normal. Consecutive enzymatic tests were evaluated in 41 participants, and 22 of them changed classifications. The variants p.(Asp444His), p.(Asp252Gly), p.[(Ala171Thr);(Asp444His)], and p.(Gln456His) were the most frequent in a total of 63 genotypes. Three new variants were identified: p.(Leu90His), p.(Ala335Val), and p.(Gly441Arg) within\u00a0 the expanded sample. The correlation between genotype and phenotype was observed in 69.89% of the cases. Chapters 2 and 3:<\/strong> In progress. Preliminary<\/strong> conclusions:<\/strong> The BTD<\/em> gene displays significant heterogeneity. The novel variants show\u00a0 evidence of pathogenicity, although further studies are needed. Despite the correlation between genotype and phenotype not always being consistent, genetic analysis can assist in cases of uncertain enzymatic results. The neonatal screening program in Brazil appears to detect a large proportion of heterozygous individuals, suggesting the need to adjust the enzymatic activity threshold. Factors such as prematurity and jaundice do not seem to significantly interfere with the genotype-phenotype discrepancy.<\/p>\n","protected":false},"excerpt":{"rendered":" 30 de setembro de 2024 (segunda-feira) – 10h30min SEMIN\u00c1RIO DE QUALIFICA\u00c7\u00c3O (Doutorado) D\u00c9VORA NATALIA RANDON Genetic Profile and Genotype-Phenotype Association for Biotinidase Deficiency in Brazil Orientadora: Dra. Ida Vanessa […]<\/p>\n","protected":false},"author":3,"featured_media":15613,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[108],"tags":[],"class_list":["post-15612","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-seminarios-e-defesas"],"_links":{"self":[{"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/posts\/15612","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/comments?post=15612"}],"version-history":[{"count":3,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/posts\/15612\/revisions"}],"predecessor-version":[{"id":15616,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/posts\/15612\/revisions\/15616"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/media\/15613"}],"wp:attachment":[{"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/media?parent=15612"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/categories?post=15612"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/tags?post=15612"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}