biostudies-literatureGonzalez-Garrido AFondo Sectorial de Investigación en Salud y Seguridad Social (FOSISS)Consejo Nacional de Ciencia y TecnologíaUniversidad Autónoma MetropolitanaParadigmas y Controversias de la Ciencia (CONACyT)F003 PCCUniversidad Autónoma Metropolitana Unidad Cuajimalpa13626https://www.ebi.ac.uk/biostudies/studies/S-EPMC9656322biostudies-literatureUnknown23(21)The clinical phenotype of <i>LMNA</i>-associated dilated cardiomyopathy (DCM) varies even among individuals who share the same mutation. <i>LMNA</i> encodes lamin AC, which interacts with the lamin-associated protein 2 alpha (LAP2α) encoded by the <i>TMPO</i> gene. The LAP2α/Arg690Cys polymorphism is frequent in Latin America and was previously found to disrupt LAP2α-Lamin AC interactions in vitro. We identified a DCM patient heterozygous for both a lamin AC truncating mutation (Ser431*) and the LAP2α/Arg690Cys polymorphism. We performed protein modeling and docking experiments, and used confocal microscopy to compare leukocyte nuclear morphology among family members with different genotype combinations (wild type, LAP2α Arg690Cys heterozygous, lamin AC/Ser431* heterozygous, and LAP2α Arg6International journal of molecular sciencesLeukocyte Nuclear Morphology Alterations in Dilated Cardiomyopathy Caused by a Lamin AC Truncating Mutation (<i>LMNA</i>/Ser431*) Are Modified by the Presence of a LAP2 Missense Polymorphism (<i>TMPO</i>/Arg690Cys).PMC965632247301018261670320221Arellanes-Robledo JRojo-Dominguez ARomero-Hidalgo SVillarreal-Molina MTCarnevale ARosendo-Gutierrez RLopez-Mora ERosas-Madrigal SGonzalez-Garrido AArregui LfalseLeukocyte Nuclear Morphology Alterations in Dilated Cardiomyopathy Caused by a Lamin AC Truncating Mutation (<i>LMNA</i>/Ser431*) Are Modified by the Presence of a LAP2 Missense Polymorphism (<i>TMPO</i>/Arg690Cys).The clinical phenotype of <i>LMNA</i>-associated dilated cardiomyopathy (DCM) varies even among individuals who share the same mutation. <i>LMNA</i> encodes lamin AC, which interacts with the lamin-associated protein 2 alpha (LAP2α) encoded by the <i>TMPO</i> gene. The LAP2α/Arg690Cys polymorphism is frequent in Latin America and was previously found to disrupt LAP2α-Lamin AC interactions in vitro. We identified a DCM patient heterozygous for both a lamin AC truncating mutation (Ser431*) and the LAP2α/Arg690Cys polymorphism. We performed protein modeling and docking experiments, and used confocal microscopy to compare leukocyte nuclear morphology among family members with different genotype combinations (wild type, LAP2α Arg690Cys heterozygous, lamin AC/Ser431* heterozygous, and LAP2α Arg62022-01-01T00:00:00Z2022 Nov2026-04-08T18:17:15.348Z2024-11-20T15:23:45.831ZS-EPMC96563223636241110.3390/ijms232113626