EVALUACIÓN CLÍNICA, BIOQUÍMICA Y MOLECULAR DE UNA FAMILIA CON RECURRENCIA DE DEFECTOS DEL TUBO NEURAL.
Abstract
Se presenta una familia originaria del sur de Nuevo León con recurrencia de defectos del tubo
neural (DTN) cuyos productos sobrevivientes se han logrado después del tratamiento preconcepcional
con folato. Después de las evaluaciones clínicas, bioquímicas y moleculares, se
encuentra que los miembros presentan heterocigocidad para la mutación MTHFR 677T y que la
madre y la hija son heterocigotas compuestas 677C/677T – 1298A/1298C. Los niveles de folatos
intraeritrocitarios y plasmáticos son normales y sólo el padre presenta niveles levemente
incrementados de homocisteinemia. Estos resultados sugieren una interacción entre factores
genéticos y nutricionales previamente implicados en la patogénesis de los DTN que podrían estar
asociados adicionalmente a la recurrencia de este cuadro malformativo.
Abstract
A family is presented it would originate of the south of Nuevo León with recurrence of neural tube
defects (NTD) whose products survivors have been achieved after the treatment preconceptional
with folate. After the clinical, biochemical and molecular evaluations, it is found that
the members present heterocigocity for the mutation MTHFR 677T and that the mother and the
daughter are compound heterozygotes 677C/677T - 1298A/1298C. The levels of red cells
folates and plasmatic they are normal and the father only presents slightly increased levels of
homocystenaemia. These results suggest an interaction among genetic and nutritional factors
previously implied additionally in the pathogenesis of the NTD that could be associate to the
recurrrrence of this defect.
Palabras clave: anancefalia, defectos, tubo, neural, Nuevo León, México, anencephaly, defects, neural, tube
Downloads
References
Lemire RJ. Neural tube defects. JAMA1988;259:558-562.
International Centre for Birth Defects, EUROCAT 1998 . World Atlas of Birth Defects. Geneva: World Health Organization; pp. 20-31.
Martínez de Villarreal LE, C Ayala-Alvarado y C Limón-Benavides 1999. Defectos congénitos y
mortalidad infantil en el estado de Nuevo León. Medicina Universitaria; 1:113-117.
Villarreal-Pérez JZ, JF González-Guerreo, JI Wong-Rios y LE Martínez de Villarreal 1999.
Actualización y reporte sobre los defectos congénitos en el Estado de Nuevo León. Secretaría
Estatal de Salud de Nuevo León. Monterrey, México
Wang Y, Y Wu, G Zhou, C Xu and K Xiao 1996. An estimate of recurrence risk for neural tube
defects in China. Hua Hsi I Ko Ta Hsueh Hsueh Pao, 27:196-198.
Carter CO and JAF Roberts 1967. The risk of recurrence after two children with central-nervoussystem malformations. Lancet; 1:306-308.
van der Put NM, RP Steegers-Theunissen, P Frosst, FJ Trijbels, TK Eskes, LP van den Heuvel,
EC Mariman, M den Heyer, R Rozen and HJ Blom.1995. Mutated methylenetetrahydrofolate
reductase as a risk factor for spina bífida. Lancet; 346: 1070-1071.
MRC Vitamin study research group. 1991. Prevention of neural-tube defects results of the
Medical Reserach Council Vitamin Study. Lancet; 338:131-137.
Czeizel AE and I Dudas 1992. Prevention of the first occurrence of neural-tube defects by
periconceptional vitamin supplementation. N Engl J Med; 327:1832-1835.
Kang SS, PW Wong, A Susmano, J Sora, M Norusis and N Ruggie.1991. Thermolabile
methylentetrahydrofolate reductase. An inherited risk factor for coronary artery disease. Am J Hum
Genet; 48: 536-545.
Engbersen AM, DG Franken, GH Boers, EM Stevens, FJ Trijbels and HJ Blom.1995.
Thermolabile 5,10-mehylentetrahydrofolate reductase as a cause of mild hyperhomocysteinemia.
Am J Hum Genet; 56:142-150.
Rosenquist TH, SA Ratashak and J Selhub.1996. Homocysteine induces congenital defects of
the heart and neural tube: effect of folic acid. Proc Natl Acad Sci U S A; 93:15227-15232.
Vanaerts LA, HJ Blom, RA Deabreu, FJ Trijbels and TK Eskes.1994. Copius Peereboom-
Stegeman JH, Noordhoek J. Prevention of neural tube defects by and toxicity of L-homocysteine in
cultured postimplantation rat embryos. Teratology; 50:348-360.
Mutchinick OM, MA Lopez, L Luna, J Waxman and VE Babinsky.1999. High prevalence of the
thermolabile methylenetetrahydrofolate reductase variant in Mexico: a country with a very high
prevalence of neural tube defects. Mol Genet Metabol; 68:461-467.
van der Put NM, F Gabreels, EM Stevens, JA Smeitink, FJ Trijbels, TK Eskes, LP van den
Heuvel and HJ Blom.1998. A second common mutation in the methylenetetrahydrofolate reductase
gene: an additional risk factor for neural-tube defects? Am J Hum Genet; 62:1044-1051.
Thompson MW, RR Mclnnes y HF Willard. 1996.Thompson Thompson Genética en
Medicina. 4a ed. Barcelona: Masson, SA. p. 337-350.
Wald NJ and A Kennard 1996. Prenatal screening for neural tube defects and Down syndrome.
In: Emery and Rimoin’s Principles and Practice of Medical Genetics. [DL Rimoin, JM Connor and
RE Pyeritz] Third edition. New York: Churchill-Livingstone; pp. 545-562.
Shaffer LG, ML Marzita, J Bodurtha, A Newlin and WE Nance.1990. Evidence for a major gene
in familial anencephaly. Am J Hum Genet; 36:97-101.
International Centre for Birth Defects, Op.cit
Mutchinick OM et. al., Op.cit
van der Put NM, RP Steegers-Theunissen et. al., Op.cit.
Ou CY, RE Stevenson, VK Brown, CE Schwartz, WP Allen, MJ Khoury, R Rozen. GP Oakley Jr
and MJ AdamsJr.1996. 5,10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk
factor for neural tube defects. Am J Med Genet; 63:610-614.
Whitehead AS, P Gallagher, JL Mills, PN Kirke, H Burke, AM Molloy, DG Weir, DC Shields, JM
Scott. 1995. A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube
defects. QJM; 88:763-766.
Shields DC, PN Kirke, JL Mills, D Ramsbottom, AM Molloy, H Burke, DG Weir, JM Scott and AS
Whitehead.1999. The "thermolabile" variant of methylentetrahydrofolate reductase and neural
defect: An evaluation of genetic risk and the relative importance of the genotypes of the embryo and
the mother. Am J Hum Genet; 64:1045-1055.
Christensen B, L Arbour, P Tran, D Leclerc, N Sabbaghian, R Platt, BM Gilfix, DS Rosenblatt,
RA Gravel, P Forbes and R Rozen 1999. Genetic polymorphisms in methylenetetrahydrofolate
reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects.
Am J Med Genet; 84:151-157.
Papapetrou C, SA Lynch, J Burn and YH Edwards 1996. Methylenetetrahydrofolate reductase
and neural tube defects. Lancet; 348:58.
Wilcken DE and XL Wang 1996. Relevance to spina bifida of mutated
methylenetetrahydrofolate reductase. Lancet; 347:340.
Mornet E, F Muller, A Lenvoise-Furet, AL Delezoide, JY Col, B Simon-Bouy and JL Serre 1997
Screening of the C677T mutation on the methylenetetrahydrofolate reductase gene in French
patients with neural tube defects. Hum Genet; 100:512-514.
Speer MC, G Worley, JF Mackey, E Melvin, WJ Oakes and TM George.1997. The thermolabile
variant of methylenetetrahydrofolate reductase (MTHFR) is not a major risk factor for neural tube
defect in American Caucasicans. Neurogenetics; 1:149-150.
de Franchis R, A Buoninconti, C Mandato, A Pepe, MP Sperandeo, R Del Gado, V Capra, E
Salvaggio, G Andria and P Mastroiacovo.1998. The C677T mutation of the 5,10-
methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy. J Med
Genet; 35:1009-1013.
Shaw GM, R Rozen, RH Finnell, CR Wasserman and EJ Lammer.1998. Maternal vitamin use,
genetic variation of infant methylenetetrahydrofolate reductase, and risk for spina bifida. Am J
Epidemiol; 148:30-31.
Koch MC, K Stegmann, A Ziegler, B Schroter and A. Ermert 1998. Evaluation of the MTHFR
C677T allele and the MTHFR gene locus in a German spina bifida population. Eur J Pediatr;
:487-492.
Ubbink JB, A Christianson, MJ Bester, MI Van Allen, PA Venter, R Delport, HJ Blom HJ, A van
der Merwe, H Potgieter and WJ Vermaak 1999. Folate status, homocysteine metabolism, and
methylene tetrahydrofolate reductase genotype in rural South African blacks with a history of
pregnancy complicated by neural tube defects. Metabolism; 48:269-274.
Boduroglu K, M Alikasifoglu, B Anar and E Tuncbilek 1999. Association of the 677C-->T
mutation on the methylenetetrahydrofolate reductase gene in Turkish patients with neural tube
defects. J Child Neurol; 14:159-161.
van der Put NM, F Gabreels, et. al. Op. cit.
Idem.
Locksmith GJ and P Duff 1998. Preventing neural tube defects: The importance of the
periconcepcional folic acid supplement. Obstet Gynecol; 91:1027-1034.
van der Put NM, F Gabreels, et. al. Op. cit.
Frosst P, HJ Blom, R Milos, P Goyette, CA Sheppard, RG Matthews, GJ Boers, M den Heijer,
LA Kluijtmans, LP van den Heuvel and R Rozen.1995. A candidate genetic risk factor for vascular
disease: a common mutation in methylenetetrahydrofolate reductase. Nat Gene ;10:111-113.
Zhao Q, RR Behringer and B de Crombrugghe 1996. Prenatal folic acid treatment suppresses
acrania and meroanencephaly in mice mutant for the Cart1 homeobox gene. Nat Genet;13:275-
Carter M, S Ulrich, Y Oofuji, DA Williams and ME Ross.1999. Crooked tail (Cd) models human
folate-responsive n
Downloads
Published
How to Cite
Issue
Section
License
The rights of the work belong to the author or authors, however, by sending it for publication in the Public Health and Nutrition Magazine of the Faculty of Public Health and Nutrition of the Autonomous University of Nuevo León, they grant the right for its first publication in between electronic, and possibly, in print to the Public Health and Nutrition Magazine. The license used is the Creative Commons attribution, which allows third parties to use what is published whenever the authorship of the work is mentioned and the first publication that is in the Public Health and Nutrition Magazine. Likewise, the author or authors will take into account that it will not be allowed to send the publication to any other journal, regardless of the format. The authors will be able to make other independent and additional contractual agreements for the non-exclusive distribution of the version of the article published in the Public Health and Nutrition Magazine (e.g., institutional repository or publication in a book) provided they clearly state that The work was published for the first time in the Public Health Magazine, Magazine of the Faculty of Public Health and Nutrition of the Autonomous University of Nuevo León.
