ISSN: 0034-8376
eISSN: 2564-8896



Exploratory Analysis of Rare and Novel Variants in Mexican Patients Diagnosed with Schizophrenia and Dementia



José J. Martínez-Magaña, Genomics Laboratory of Psychiatric and Neurodegenerative Diseases, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Alma D. Genís-Mendoza, Genomics Laboratory of Psychiatric and Neurodegenerative Diseases, Instituto Nacional de Medicina Genómica, Mexico City; Psychiatric Care Services, Hospital Psiquiátrico Infantil "Juan N. Navarro", SSA, Mexico City; Mexico
Vanessa González-Covarrubias, Pharmacogenomics Laboratory, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Janet Jiménez-Guenchi, Psychiatric Care Services, Hospital Psiquiátrico "Fray Bernardino Alvarez", SSA, Mexico City, Mexico
Aidé G. Galindo-Chávez, Psychiatric Care Services, Hospital Psiquiátrico "Fray Bernardino Alvarez", SSA, Mexico City, Mexico
Andrés Roche-Bergua, Psychiatric Care Services, Hospital Psiquiátrico "Fray Bernardino Alvarez", SSA, Mexico City, Mexico
Carlos Castañeda-González, Psychiatric Care Services, Hospital Psiquiátrico "Fray Bernardino Alvarez", SSA, Mexico City, Mexico
Nuria Lanzagorta, Grupo de Estudios Médicos y Familiares, Mexico City, Mexico
Xavier Soberón, Pharmacogenomics Laboratory, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Humberto Nicolini, Genomics Laboratory of Psychiatric and Neurodegenerative Diseases, Instituto Nacional de Medicina Genómica, Mexico City, Grupo de Estudios Médicos y Familiares, Mexico City, Mexico


Background: Schizophrenia (SCZ) and dementia, often related, are two of the most common neuropsychiatric diseases; epidemiological studies have shown that SCZ patients present a 2-fold increased risk for dementia compared to non-schizophrenic individuals. We explored the presence of rare and novel damaging gene variants in patients diagnosed with late-onset dementia of Alzheimer’s type (DAT) or SCZ. Methods: We included 7 DAT and 12 SCZ patients and performed high-depth targeted sequencing of 184 genes. Results: We found novel and rare damaging variants in 18 genes in these Mexican patients. Carriers o these variants showed extreme phenotypes, including, treatment-resistant SCZ or cognitive decline. Furthermore, we found a variation on ABCC1 as a possible link between psychosis and cognitive impairment. Discussion: As an exploratory analysis, we report some interesting variations that should be corroborated in larger sample size studies. (REV INVEST CLIN. 2019;71:246-54)



Keywords: Next-generation sequencing. Dementia. Schizophrenia. Novel variants. Rare variants.