RESUMO
BACKGROUND: Recently, a novel mutation in exon 24 of DNAJC13 gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi-incident Mennonite family. METHODS: In the present study the mutation containing exon of the DNAJC13 gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD). RESULTS: Our sequence analysis did not identify any coding variants in exon 24 of DNAJC13. Two previously described variants in intron 23 (rs200204728 and rs2369796) were observed. CONCLUSION: Our results indicate that the region surrounding the DNAJC13 p.Asn855Ser substitution is highly conserved and mutations in this exon are not a common cause of PD or LBD among Caucasian populations.
Assuntos
Doença por Corpos de Lewy/genética , Chaperonas Moleculares/genética , Doença de Parkinson/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
FUS/TLS (denoting fused in sarcoma/translocated in liposarcoma [MIM 137070]) codifies an RNA binding protein. Mutations in this gene cause amyotrophic lateral sclerosis (ALS; MIM 608030). Essential tremor (ET [MIM 190300]) is the most frequent movement disorder. Despite its strong familiar aggregation, recently a whole exome sequencing study has identified FUS mutations as a cause of familial ET. To determine whether mutations in FUS are also common in other populations, we sequenced FUS gene in 178 unrelated Spanish subjects with ET. We detected only an intronic single-pair nucleotide deletion (c.1293-37delC), which was predicted to affect mRNA splicing. However, leukocyte mRNA analysis showed no changes in FUS expression. In conclusion, coding or splicing FUS mutations are not a frequent cause of ET in the Spanish population.
Assuntos
Tremor Essencial/etnologia , Tremor Essencial/genética , Exoma/genética , Taxa de Mutação , Mutação , Proteína FUS de Ligação a RNA/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases/genética , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Expressão Gênica , Humanos , Leucócitos , Masculino , Pessoa de Meia-Idade , Splicing de RNA/genética , RNA Mensageiro/genética , Deleção de Sequência/genética , Espanha/etnologia , População Branca/genética , Adulto JovemRESUMO
Despite the research, few advances in the etiopathogenesis on essential tremor (ET) have been made to date. The high frequency of positive family history of ET and the observed high concordance rates in monozygotic compared with dizygotic twins support a major role of genetic factors in the development of ET. In addition, a possible role of environmental factors has been suggested in the etiology of ET (at least in non-familial forms). Although several gene variants in the LINGO1 gene may increase the risk of ET, to date no causative mutated genes have been identified. In this review, we summarize the studies performed on families with tremor, twin studies, linkage studies, case-control association studies, and exome sequencing in familial ET.
Assuntos
Tremor Essencial/etiologia , Tremor Essencial/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Bases de Dados Bibliográficas/estatística & dados numéricos , Tremor Essencial/epidemiologia , Humanos , Proteínas de Membrana/genética , Mutação/genética , Proteínas do Tecido Nervoso/genética , Estudos em Gêmeos como AssuntoRESUMO
BACKGROUND: Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome-wide association study has recently shown that LINGO1 gene variants are associated with increased risk of ET. METHODS: We intended to replicate these findings by genotyping rs9652490 and rs11856808 in a series of 226 familial ET subjects and 1117 healthy controls from referral movement disorder clinics in Spain. RESULTS: We were unable to replicate the association between LINGO1 variants and familial ET. CONCLUSIONS: Our results indicate that the LINGO1 variants analyzed are not a major risk factor for developing familial ET in our population, which suggests the existence of other unknown genetic risk factors responsible for familial ET in the Spanish population.