Analysis of FMO3 gene variants in Argentine patients: Implications for the diagnosis of Trimethylaminuria.

Primary trimethylaminuria (TMAu), also known as "fishy odor syndrome" is a metabolic condition characterized by the inability of flavin-monooxygenase 3 (FMO3) to convert foul-smelling trimethylamine (TMA) into odorless TMA N-oxide. The presence of TMA in the body fluids of affected individ...

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Detalles Bibliográficos
Autores principales: Silvera Ruiz, SM, Grosso, CL, Castro, GM, Dodelson de Kremer, R, Angaroni , CJ
Formato: Artículo revista
Lenguaje:Español
Publicado: Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2023
Materias:
Trimethylaminuria
FMO3
Trimethylamine
TRIMETIAMINURIA
TRIMETILAMINA
Acceso en línea:https://revistas.unc.edu.ar/index.php/med/article/view/42658
Aporte de:
Revista de la Facultad de Ciencias Médicas de Córdoba de Universidad Nacional de Córdoba
id I10-R327-article-42658
record_format ojs
institution Universidad Nacional de Córdoba
institution_str I-10
repository_str R-327
container_title_str Revista de la Facultad de Ciencias Médicas de Córdoba
language Español
format Artículo revista
topic Trimethylaminuria
FMO3
Trimethylamine
TRIMETIAMINURIA
FMO3
TRIMETILAMINA
spellingShingle Trimethylaminuria
FMO3
Trimethylamine
TRIMETIAMINURIA
FMO3
TRIMETILAMINA
Silvera Ruiz, SM
Grosso, CL
Castro, GM
Dodelson de Kremer, R
Angaroni , CJ
Analysis of FMO3 gene variants in Argentine patients: Implications for the diagnosis of Trimethylaminuria.
topic_facet Trimethylaminuria
FMO3
Trimethylamine
TRIMETIAMINURIA
FMO3
TRIMETILAMINA
author Silvera Ruiz, SM
Grosso, CL
Castro, GM
Dodelson de Kremer, R
Angaroni , CJ
author_facet Silvera Ruiz, SM
Grosso, CL
Castro, GM
Dodelson de Kremer, R
Angaroni , CJ
author_sort Silvera Ruiz, SM
title Analysis of FMO3 gene variants in Argentine patients: Implications for the diagnosis of Trimethylaminuria.
title_short Analysis of FMO3 gene variants in Argentine patients: Implications for the diagnosis of Trimethylaminuria.
title_full Analysis of FMO3 gene variants in Argentine patients: Implications for the diagnosis of Trimethylaminuria.
title_fullStr Analysis of FMO3 gene variants in Argentine patients: Implications for the diagnosis of Trimethylaminuria.
title_full_unstemmed Analysis of FMO3 gene variants in Argentine patients: Implications for the diagnosis of Trimethylaminuria.
title_sort analysis of fmo3 gene variants in argentine patients: implications for the diagnosis of trimethylaminuria.
description Primary trimethylaminuria (TMAu), also known as "fishy odor syndrome" is a metabolic condition characterized by the inability of flavin-monooxygenase 3 (FMO3) to convert foul-smelling trimethylamine (TMA) into odorless TMA N-oxide. The presence of TMA in the body fluids of affected individuals results in body odor causing severe psychosocial problems. Secondary trimethylaminuria differs from primary trimethylaminuria in that it is related to other underlying conditions, such as liver, kidney, or metabolic diseases, not genetic. The present work aims to analyze variants of the FMO3 gene in Argentinean patients with a phenotype suggestive of TMAu. Genomic DNA from 22 patients was extracted from whole blood with the Roche MagNA Pure system. All coding exons of the FMO3 gene and adjacent intron sequences were amplified by polymerase chain reaction (PCR). Sequencing was performed on both DNA strands by direct sequencing (ABI 3130XL, Applied Biosystems). In this cohort, 15 variants in the FMO3 gene were identified: 5 non-synonymous, 8 intronic, and 2 synonymous. The missense changes p.Glu158Lys, p.Glu308Gly, p.Arg387His, p.Val257Met, and p.Ala458Val have been previously described in patients with TMAu except for the p.Ala458Val variant. The diagnosis of primary TMAu was established in 4 individuals (18%). Of the remaining patients, no changes in FMO3 were detected in 5 (22%), and 13 (59%) had gene alterations that could be causative or predisposing to TMAu, but without reaching a diagnostic definition. This is the first molecular study of fish odor syndrome in a cohort of Argentinean patients, and it allowed us to establish the genetic diagnosis of primary TMAu in our environment. The results obtained include the identification of a new variant, p.Ala458Val, with a possible pathogenic effect on the FMO3 protein. The recognition of this socially disabling disease in Argentina should alert specialists to its suspicion and highlight the need for effective therapeutic advances.
publisher Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
publishDate 2023
url https://revistas.unc.edu.ar/index.php/med/article/view/42658
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spelling I10-R327-article-426582023-10-19T21:20:16Z Analysis of FMO3 gene variants in Argentine patients: Implications for the diagnosis of Trimethylaminuria. Análisis de variantes del gen FMO3 en pacientes argentinos: Implicancias para el diagnóstico de Trimetilaminuria Silvera Ruiz, SM Grosso, CL Castro, GM Dodelson de Kremer, R Angaroni , CJ Trimethylaminuria FMO3 Trimethylamine TRIMETIAMINURIA FMO3 TRIMETILAMINA Primary trimethylaminuria (TMAu), also known as "fishy odor syndrome" is a metabolic condition characterized by the inability of flavin-monooxygenase 3 (FMO3) to convert foul-smelling trimethylamine (TMA) into odorless TMA N-oxide. The presence of TMA in the body fluids of affected individuals results in body odor causing severe psychosocial problems. Secondary trimethylaminuria differs from primary trimethylaminuria in that it is related to other underlying conditions, such as liver, kidney, or metabolic diseases, not genetic. The present work aims to analyze variants of the FMO3 gene in Argentinean patients with a phenotype suggestive of TMAu. Genomic DNA from 22 patients was extracted from whole blood with the Roche MagNA Pure system. All coding exons of the FMO3 gene and adjacent intron sequences were amplified by polymerase chain reaction (PCR). Sequencing was performed on both DNA strands by direct sequencing (ABI 3130XL, Applied Biosystems). In this cohort, 15 variants in the FMO3 gene were identified: 5 non-synonymous, 8 intronic, and 2 synonymous. The missense changes p.Glu158Lys, p.Glu308Gly, p.Arg387His, p.Val257Met, and p.Ala458Val have been previously described in patients with TMAu except for the p.Ala458Val variant. The diagnosis of primary TMAu was established in 4 individuals (18%). Of the remaining patients, no changes in FMO3 were detected in 5 (22%), and 13 (59%) had gene alterations that could be causative or predisposing to TMAu, but without reaching a diagnostic definition. This is the first molecular study of fish odor syndrome in a cohort of Argentinean patients, and it allowed us to establish the genetic diagnosis of primary TMAu in our environment. The results obtained include the identification of a new variant, p.Ala458Val, with a possible pathogenic effect on the FMO3 protein. The recognition of this socially disabling disease in Argentina should alert specialists to its suspicion and highlight the need for effective therapeutic advances. La trimetilaminuria primaria (TMAu), también conocida como "síndrome del olor a pescado", es una afección metabólica caracterizada por la incapacidad de la flavin-monooxigenasa 3 (FMO3) para convertir la trimetilamina (TMA), de olor desagradable, en N-óxido de TMA inodoro. La presencia de TMA en fluidos corporales de los individuos afectados produce el mal olor corporal causando graves problemas psicosociales. La trimetilaminuria secundaria se diferencia de la primaria en que está relacionada con otras condiciones subyacentes, como enfermedades hepáticas, renales o metabólicas, no genéticas. El objetivo del presente trabajo es el análisis de variantes del gen FMO3 en pacientes argentinos con fenotipo sugestivo de TMAu El ADN genómico de 22 pacientes fue extraído de sangre entera con el sistema MagNA Pure de Roche. Todos los exones codificantes del gen FMO3 y las secuencias de intrones adyacentes se amplificaron mediante la reacción en cadena de la polimerasa (PCR). La secuenciación se llevó a cabo en ambas cadenas de ADN mediante secuenciación directa (ABI 3130XL, Applied Biosystems). En esta cohorte se identificaron 15 variantes en el gen FMO3: 5 no sinónimas, 8 intrónicas y 2 sinónimas. Los cambios missense p.Glu158Lys, p.Glu308Gly, p.Arg387His, p.Val257Met y p.Ala458Val han sido previamente descriptas en pacientes con TMAu excepto la variante p.Ala458Val. El diagnóstico de TMAu primaria se estableció en 4 individuos (18%). Del resto de los pacientes, en 5 (22%) no se detectaron cambios en FMO3, y 13 (59%) presentan alteraciones génicas que podrían ser causales o predisponen a TMAu,  pero sin llegar a una definición diagnóstica. Este es el primer estudio molecular sobre síndrome del olor a pescado en una cohorte de pacientes argentinos y permitió establecer el diagnóstico genético de TMAu primaria en nuestro medio. Entre los resultados obtenidos se destaca la identificación de una nueva variante, la p.Ala458Val, con posible efecto patogénico en la proteína FMO3. El reconocimiento de esta enfermedad socialmente incapacitante en Argentina debería alertar a los especialistas para su sospecha y evidenciar la necesidad de avances terapéuticos efectivos. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2023-10-19 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion application/pdf https://revistas.unc.edu.ar/index.php/med/article/view/42658 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 80 (2023): Suplemento JIC XXIV Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 80 (2023): Suplemento JIC XXIV Revista da Faculdade de Ciências Médicas de Córdoba; v. 80 (2023): Suplemento JIC XXIV 1853-0605 0014-6722 spa https://revistas.unc.edu.ar/index.php/med/article/view/42658/42858 Derechos de autor 2023 Universidad Nacional de Córdoba http://creativecommons.org/licenses/by-nc/4.0

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