Maria Teresa Tusié-Luna

Publications of Maria Teresa Tusié-Luna

• SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome.

  Authors: Argelia Medeiros-Domingo, Toshihiko Kaku, David J Tester, Pedro Iturralde Torres, Ajit Itty, Bin Ye, Carmen Valdivia, Kazuo Ueda, Samuel Canizales-Quinteros, Maria Teresa Tusié-Luna, Jonathan C Makielski, Michael J Ackerman

  Circulation. 08/2007; 116(2):134-42.

  BACKGROUND: Congenital long-QT syndrome (LQTS) is potentially lethal secondary to malignant ventricular arrhythmias and is caused predominantly by mutations in genes that encode cardiac ion channels.BACKGROUND: Congenital long-QT syndrome (LQTS) is potentially lethal secondary to malignant ventricular arrhythmias and is caused predominantly by mutations in genes that encode cardiac ion channels. Nearly 25% of patients remain without a genetic diagnosis, and genes that encode cardiac channel regulatory proteins represent attractive candidates. Voltage-gated sodium channels have a pore-forming alpha-subunit associated with 1 or more auxiliary beta-subunits. Four different beta-subunits have been described. All are detectable in cardiac tissue, but none have yet been linked to any heritable arrhythmia syndrome. METHODS AND RESULTS: We present a case of a 21-month-old Mexican-mestizo female with intermittent 2:1 atrioventricular block and a corrected QT interval of 712 ms. Comprehensive open reading frame/splice mutational analysis of the 9 established LQTS-susceptibility genes proved negative, and complete mutational analysis of the 4 Na(vbeta)-subunits revealed a L179F (C535T) missense mutation in SCN4B that cosegregated properly throughout a 3-generation pedigree and was absent in 800 reference alleles. After this discovery, SCN4B was analyzed in 262 genotype-negative LQTS patients (96% white), but no further mutations were found. L179F was engineered by site-directed mutagenesis and heterologously expressed in HEK293 cells that contained the stably expressed SCN5A-encoded sodium channel alpha-subunit (hNa(V)1.5). Compared with the wild-type, L179F-beta4 caused an 8-fold (compared with SCN5A alone) and 3-fold (compared with SCN5A + WT-beta4) increase in late sodium current consistent with the molecular/electrophysiological phenotype previously shown for LQTS-associated mutations. CONCLUSIONS: We provide the seminal report of SCN4B-encoded Na(vbeta)4 as a novel LQT3-susceptibility gene.

• Mutations in MODY genes are not common cause of early-onset type 2 diabetes in Mexican families.

  Authors: Aarón Domínguez-López, Angel Miliar-García, Yayoi X Segura-Kato, Laura Riba, Riba Esparza-López, Salvador Ramírez-Jiménez, Maribel Rodríguez-Torres, Samuel Canizales-Quinteros, Siraam Cabrera-Vásquez, Verónica Fragoso-Ontiveros, Carlos A Aguilar-Salinas, Nelly Altamirano-Bustamante, Raúl Calzada-León, Carlos Robles-Valdés, Luz E Bravo-Ríos, Maria Teresa Tusié-Luna

  JOP : Journal of the pancreas. 06/2005; 6(3):238-45.

  CONTEXT: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset and a primary insulin secretionCONTEXT: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset and a primary insulin secretion defect. Certain MODY gene sequence variants may be involved in polygenic forms of type 2 diabetes. OBJECTIVE: We assessed the contribution of MODY genes to the etiology of type 2 early-onset diabetes in 23 Mexican families, including five with apparently autosomal dominant inheritance. PATIENTS: Twenty-three unrelated Mexican families with early-onset type 2 diabetes previously screened for the presence of glucokinase mutations, were studied. DESIGN: We screened MODY genes for sequence variants by PCR-SSCP analysis and automated sequencing. We performed a functional analysis of the HNF-1alpha P379H recombinant protein in vitro in both HeLa and RINm5f beta-cell lines. MAIN OUTCOME MEASURES: MODY gene mutation screening and P379H mutant protein transactivation assay. RESULTS: No mutations were detected in the HNF-4alpha, IPF-1, NEUROD1 or HNF-1beta genes in any of the families studied. A new mutation (P379H) of the HNF-1alpha gene was identified in one MODY family. RINm5f and HeLa cell transfection assays revealed decreased transactivation activity of the mutant protein on the human insulin promoter. CONCLUSIONS: All known MODY genes were screened for abnormalities in this cohort of early-onset diabetes families which included 5 MODY pedigrees. We identified a new HNF-1alpha MODY mutation (P379H) and demonstrated that it reduces the transactivation potential of the mutant protein on the human insulin promoter. No other mutation was identified in this cohort indicating that abnormalities in MODY genes are generally not a common cause of early-onset diabetes and this includes MODY families in Mexico.

• Locus on chromosome 6p linked to elevated HDL cholesterol serum levels and to protection against premature atherosclerosis in a kindred with familial hypercholesterolemia.

  Authors: Samuel Canizales-Quinteros, Carlos A Aguilar-Salinas, Eduardo Reyes-Rodríguez, Laura Riba, Maribel Rodríguez-Torres, Salvador Ramírez-Jiménez, Adriana Huertas-Vázquez, Verónica Fragoso-Ontiveros, Alejandro Zentella-Dehesa, José L Ventura-Gallegos, Gerardo Vega-Hernández, Angelina López-Estrada, Moisés Aurón-Gómez, Francisco Gómez-Pérez, Juan Rull, Nancy J Cox, Graeme I Bell, Maria Teresa Tusié-Luna

  Circulation research. 04/2003; 92(5):569-76.

  Heterozygous familial hypercholesterolemia (FH) is a highly atherogenic genetic disorder leading to premature coronary heart disease (CHD), usually before 60 years of age. We studied an extendedHeterozygous familial hypercholesterolemia (FH) is a highly atherogenic genetic disorder leading to premature coronary heart disease (CHD), usually before 60 years of age. We studied an extended multigenerational kindred with FH linked to chromosome 1p32 in which atherosclerotic complications were either delayed or prevented in individuals with elevated HDL cholesterol (HDL-C) levels or hyperalphalipoproteinemia (HA). Premature CHD was observed in FH individuals without HA. The study of this family established that the HA trait in the family also followed an autosomal dominant mode of inheritance with a pattern of segregation independent from FH. We identified a locus on chromosome 6 linked to elevated HDL-C levels (HA) in this family. Haplotype analysis refined the localization to a 7.32-cM interval (73 to 80 cM from pter) flanked by markers D6S1280 and D6S1275. Parametric 2-point and multipoint analyses yielded maximum LOD scores of 3.05 and 3.17, respectively. This finding was confirmed with a nonparametric multipoint score of 3.78 (P=0.0009). We propose that this locus, linked to elevated HDL-C levels, confers protection against premature CHD within an FH context.

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• With the finished human genome in hand, what next?

  Authors: Julio Collado-Vides, Arturo Medrano-Soto, Maria Teresa Tusié-Luna

  Genome biology. 02/2003; 4(7):328.