MUTACIONES EN EL GEN LCAT Y HETEROGENEIDAD CLÍNICA: MAPEO DE CORRELACIONES GENOTIPO-FENOTIPO
DOI:
https://doi.org/10.66104/9ty4ma64Palabras clave:
Heterogeneidad Genética, Deficiencia de Lecitina Colesterol Aciltransferasa, Enfermedad Plantar, Lecitina Colesterol Aciltransferasa, Enfermedades RarasResumen
La deficiencia de lecitina-colesterol aciltransferasa (LCAT) es un trastorno autosómico recesivo poco frecuente que se caracteriza por una heterogeneidad genética y fenotípica significativa. Se han identificado más de 100 mutaciones diferentes en el gen LCAT, lo que resulta en dos fenotipos clínicos distintos: deficiencia familiar de LCAT (FLD) y enfermedad de ojo de pez (FED). Este estudio tuvo como objetivo realizar una revisión bibliográfica integradora para identificar y caracterizar mutaciones en el gen LCAT, enfatizando las correlaciones genotipo-fenotipo y los mecanismos que determinan la variabilidad clínica. Se realizó una búsqueda activa en bases de datos electrónicas (PubMed, MedLine, SciELO y LILACS) entre enero de 2011 y diciembre de 2025, siguiendo las recomendaciones PRISMA. La selección de los estudios fue realizada por dos revisores independientes, analizando títulos, resúmenes y textos completos, aplicando criterios de inclusión y exclusión predefinidos. Se incluyeron diecinueve estudios que describían mutaciones específicas, fenotipos clínicos y datos bioquímicos. Los resultados demuestran una variación significativa en la distribución de mutaciones de cambio de sentido, sin sentido y de desplazamiento del marco de lectura a lo largo del gen LCAT. Se observó una notable heterogeneidad fenotípica, ya que pacientes con genotipos idénticos presentaron manifestaciones clínicas distintas, incluyendo variaciones en la afectación renal, manifestaciones oftalmológicas, anemia y perfil lipídico. Se identificó un efecto fundador en poblaciones aisladas, particularmente en familias brasileñas de Piauí. La correlación genotipo-fenotipo no es lineal, lo que sugiere un papel importante de los factores modificadores genéticos, ambientales y epigenéticos. Estos hallazgos contribuyen a una mejor comprensión de los mecanismos moleculares y clínicos de la deficiencia de LCAT, fundamental para futuros enfoques diagnósticos y terapéuticos en enfermedades raras.
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Derechos de autor 2026 Higo José Neri da Silva , Ester Pereira Miranda, Deylane Menezes Teles e Oliveira , Keylla da Conceição Machado, Kátia da Conceição Machado, Pedro Agnel Dias Miranda Neto, Geyza Caroline Oliveira Pinto , Adalberto Socorro da Silva
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