RESUMO
Pathogenic variants in PRKN cause early-onset Parkinson's disease (PD), while the role of alpha-synuclein in PRKN-PD remains uncertain. One study performed a blood-based alpha-synuclein seed amplification assay (SAA) in PRKN-PD, not detecting seed amplification in 17 PRKN-PD patients. By applying a methodologically different SAA focusing on neuron-derived extracellular vesicles, we demonstrated alpha-synuclein seed amplification in 8 of 13 PRKN-PD patients, challenging the view of PRKN-PD as a non-synucleinopathy. Moreover, we performed blinded replication of the neuron-derived extracellular vesicles-dependent SAA in idiopathic PD patients and healthy controls. In conclusion, blood-based neuron-derived extracellular vesicles-dependent SAA represents a promising biomarker to elucidate the underpinnings of (monogenic) PD. ANN NEUROL 2024;95:1173-1177.
Assuntos
Doença de Parkinson , alfa-Sinucleína , Humanos , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Doença de Parkinson/genética , Doença de Parkinson/patologia , Doença de Parkinson/metabolismo , Feminino , Masculino , Biomarcadores/sangue , Biomarcadores/metabolismo , Pessoa de Meia-Idade , Idoso , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Neurônios/metabolismo , Neurônios/patologiaRESUMO
Patients with mutations in DJ-1 have early-onset Parkinson's disease and slow progression. Here we describe a Turkish family with a large deletion in the neighboring genes DJ-1 (del exons 1-5) and TNFRSF9 (del exons 1-6), raising the question if TNFRSF9 is a possible disease modifier.
Assuntos
Doença de Parkinson , Proteína Desglicase DJ-1 , Deleção de Sequência , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral , Idade de Início , Éxons , Humanos , Doença de Parkinson/genética , Proteína Desglicase DJ-1/genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genéticaRESUMO
BACKGROUND: The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. OBJECTIVE: To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. METHODS: Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. RESULTS: Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. CONCLUSION: With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society.
Assuntos
Atrofia Óptica , Ataxias Espinocerebelares , Degenerações Espinocerebelares , Humanos , Espasticidade Muscular , Turquia/epidemiologiaRESUMO
Objective: The aim of this research was to determine the association between the fok1 polymorphism and uterine leiomyomas. Material and Methods: For genotyping the fok1 polymorphism of the vitamin D receptor, real-time polymerase chain reaction was performed on blood samples of uterine leiomyoma (n=27) and control (n=33) groups. For statistical analyses, SPSS v.23 software (SPSS Inc., Chicago, IL, USA) was used. Results: A statistically significant difference was observed for the frequency of the CC genotype between the uterine leiomyoma and control groups, and the frequencies of the T allele in the uterine leiomyoma groups were significantly higher than in the control group. CONCLUSION: The presence of the fok1 CC genotype may be a risk-reducing factor and the T allele may be a potential risk factor for developing uterine leiomyoma.