Analysis of select folate pathway genes, PAX3, and human T in a Midwestern neural tube defect population.

Trembath, D; Sherbondy, A L; Vandyke, D C; Shaw, G M; Todoroff, K; Lammer, E J; Finnell, R H; Marker, S; Lerner, G; Murray, J C

Trembath, D; Sherbondy, A L; Vandyke, D C; Shaw, G M; Todoroff, K; Lammer, E J; Finnell, R H; Marker, S; Lerner, G; Murray, J C.

Afiliación

Trembath D; Department of Pediatrics, University of Iowa, Iowa City 52242-1083, USA.

Teratology ; 59(5): 331-41, 1999 May.

Article en En | MEDLINE | ID: mdl-10332959

RESUMEN

Neural tube defects (NTDs) are a common birth defect, seen in approximately 1/1,000 births in the United States. NTDs are considered a complex trait where several genes, interacting with environmental factors, create the phenotype. Using a Midwestern NTD population consisting of probands, parents, and siblings from Iowa, Minnesota, and Nebraska, we analyzed a range of candidate genes, including 5,10-methylenetetrahydrofolate reductase (MTHFR), folate receptors-alpha (FOLR1; hereafter abbreviated "FR-alpha") and -beta (FOLR2; hereafter, "FR-beta"), methionine synthase (hereinafter, "MS"), T, the human homolog of the murine Brachyury gene, and the paired-box homeotic gene 3 (PAX3), for association with NTDs. We were unable to demonstrate an association using a previously described Ala-->Val mutation in MTHFR and the majority of our NTD populations. However, we discovered a silent polymorphism in exon 6 of MTHFR which conserved a serine residue and which showed significant association with NTDs in our Iowa population. Analysis of exon 7 of MTHFR then demonstrated an Ala-->Glu mutation which was significantly associated with our Iowa NTD population; however, we could not replicate this result either in a combined Minnesota/ Nebraska or in a California NTD population. Using polymorphic markers for MS, FR-beta, T, and PAX3, we were unable to demonstrate linkage disequilibrium with our NTD populations. A mutation search of FR-alpha revealed one proband with a de novo silent mutation of the stop codon. This work provides a new panel of genetic variants for studies of folate metabolism and supports, in some NTD populations, an association between MTHFR and NTDs.

Asunto(s)

5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética; Proteínas de Unión al ADN/genética; Proteínas Fetales; Ácido Fólico/metabolismo; Proteínas de Homeodominio/genética; Defectos del Tubo Neural/genética; Receptores de Superficie Celular; Proteínas de Dominio T Box; Factores de Transcripción/genética; 5,10-Metilenotetrahidrofolato Reductasa (FADH2); Alelos; Animales; Secuencia de Bases; Proteínas Portadoras/genética; Exones; Receptor 1 de Folato; Receptores de Folato Anclados a GPI; Ácido Fólico/genética; Frecuencia de los Genes; Humanos; Desequilibrio de Ligamiento; Metilenotetrahidrofolato Reductasa (NADPH2); Ratones; Medio Oeste de Estados Unidos; Datos de Secuencia Molecular; Mutación; Defectos del Tubo Neural/metabolismo; Oxidorreductasas/genética; Factor de Transcripción PAX3; Factores de Transcripción Paired Box; Polimorfismo Genético

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa / Factores de Transcripción / Receptores de Superficie Celular / Proteínas de Homeodominio / Proteínas de Dominio T Box / Proteínas de Unión al ADN / Proteínas Fetales / Ácido Fólico / Defectos del Tubo Neural Límite: Animals / Humans País/Región como asunto: America do norte Idioma: En Revista: Teratology Año: 1999 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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