RESUMEN
BACKGROUND: Hereditary transthyretin (ATTRv) p.Val142Ile (V122I) mutation is the most common inherited cause of cardiac amyloidosis and little is known about the phenotype and outcome of the rare homozygotic genotype. This study aimed to compare phenotypic characteristics and outcomes between heterozygous and homozygous patients with ATTRv V122I amyloidosis. MATERIAL AND METHODS: This monocentric, observational, retrospective study conducted at the French National Referral Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil), described clinical, electrocardiographic, cardiac imaging features and prognostic data for patients with ATTRv V122I amyloidosis. RESULTS: Among 185 ATTRv V122I patients identified, 161 were heterozygous and 24 were homozygous. The homozygous frequency was 13%. Onset occured significantly earlier in the homozygotes compared to heterozygotes with earlier median age at diagnosis (67[63-71] years vs 76[70-79] years, p < .001), age at first cardiac symptom (66[61-71] years vs 74[68-78] years, p < .001) and age at first extracardiac symptom (59[52-70] years vs 69[62-75] years, p = .003). Homozygous ATTRv V122I was also associated with greater disease burden with earlier events (death, transplant or hospitalisation for acute heart failure) compared with heterozygotes (71[67-74] vs 78[76-79] years, p = .018). CONCLUSION: This rare, homozygous V122I cohort confirmed the earlier age of onset, death and cardiac events in this population.
Asunto(s)
Neuropatías Amiloides Familiares , Prealbúmina , Humanos , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Homocigoto , Heterocigoto , Estudios Retrospectivos , Prealbúmina/genética , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/complicacionesAsunto(s)
Canalopatías/genética , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/genética , Trombosis/genética , Anemia Hemolítica Congénita/complicaciones , Anemia Hemolítica Congénita/genética , Anemia Hemolítica Congénita/patología , Canalopatías/complicaciones , Canalopatías/patología , Eritrocitos/patología , Mutación con Ganancia de Función , Hemólisis , Humanos , Masculino , Persona de Mediana Edad , Mutación Puntual , Trombosis/complicaciones , Trombosis/patologíaAsunto(s)
ATPasas Asociadas con Actividades Celulares Diversas/genética , Anemia Hemolítica Congénita/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Trastornos del Neurodesarrollo/genética , ATPasas de Translocación de Protón Vacuolares/genética , Anemia Hemolítica Congénita/patología , Médula Ósea/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Preescolar , Heterocigoto , Humanos , Amaurosis Congénita de Leber/genética , Amaurosis Congénita de Leber/patología , Imagen por Resonancia Magnética , Masculino , Mutación Missense , Trastornos del Neurodesarrollo/patología , Neuroimagen , Recuento de Reticulocitos , Secuenciación Completa del GenomaRESUMEN
Studies of the phenotype and population distribution of rare genetic forms of parkinsonism are required, now that gene-targeting approaches for Parkinson disease have reached the clinical trial stage. We evaluated the frequencies of PRKN, PINK1, and DJ-1 mutations in a cohort of 1,587 cases. Mutations were found in 14.1% of patients; 27.6% were familial and 8% were isolated. PRKN was the gene most frequently mutated in Caucasians, whereas PINK1 mutations predominated in Arab-Berber individuals. Patients with PRKN mutations had an earlier age at onset, and less asymmetry, levodopa-induced motor complications, dysautonomia, and dementia than those without mutations. ANN NEUROL 2020;88:843-850.
