RESUMO
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.
Assuntos
Neuropatias Amiloides Familiares , Pré-Albumina , Humanos , Pessoa de Meia-Idade , Idoso , Estudos de Coortes , Homozigoto , Heterozigoto , Estudos Retrospectivos , Pré-Albumina/genética , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/complicaçõesAssuntos
Canalopatias/genética , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/genética , Trombose/genética , Anemia Hemolítica Congênita/complicações , Anemia Hemolítica Congênita/genética , Anemia Hemolítica Congênita/patologia , Canalopatias/complicações , Canalopatias/patologia , Eritrócitos/patologia , Mutação com Ganho de Função , Hemólise , Humanos , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Trombose/complicações , Trombose/patologiaAssuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Anemia Hemolítica Congênita/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Transtornos do Neurodesenvolvimento/genética , ATPases Vacuolares Próton-Translocadoras/genética , Anemia Hemolítica Congênita/patologia , Medula Óssea/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Pré-Escolar , Heterozigoto , Humanos , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/patologia , Imageamento por Ressonância Magnética , Masculino , Mutação de Sentido Incorreto , Transtornos do Neurodesenvolvimento/patologia , Neuroimagem , Contagem de Reticulócitos , Sequenciamento Completo do GenomaRESUMO
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.