RESUMEN
BACKGROUND AND PURPOSE: Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative diseases. Mutations in the spastin (SPG4) gene are responsible for approximately 40% of autosomal dominant HSP (AD-HSP) and 6.5-18% of sporadic cases. METHODS: Spastin mutations were screened in 11 AD-HSP families and 11 sporadic cases by direct sequencing and MLPA assay. Novel mutations were detected in 100 healthy controls by PCR-RFLP. RESULTS: We identified seven different spastin mutations in five probands and one sporadic patient. Two of seven mutations were novel. The c.458delT was a pathogenic mutation, but the effect of c.1724 G>T remained unknown. CONCLUSIONS: This study allowed us to estimate the frequency of the SPG4 mutations in Chinese at 45% (5/11) in families with AD-HSP and 9% (1/11) in sporadic cases. In addition, our data showed p.T614I was not associated with congenital arachnoid cysts.
Asunto(s)
Adenosina Trifosfatasas/genética , Pueblo Asiatico/genética , Paraplejía Espástica Hereditaria/genética , Adolescente , Adulto , Secuencia de Bases , Niño , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa Multiplex , Linaje , Polimorfismo de Longitud del Fragmento de Restricción , EspastinaRESUMEN
OBJECTIVE - Genome-wide association study (GWAS) has identified a variant in LINGO1 (rs9652490) that increases the risk of essential tremor (ET) among Caucasians. It has been suggested that among Asians, the risk variant is relevant only for the familial forms of ET. We investigated the association of the rs9652490 variant with sporadic and familial ET in a Chinese population and conducted a pooled analysis to compare the potential differential effect between sporadic and familial ET. METHODS - rs9652490 was genotyped by direct sequencing in 117 ET and 160 controls in a Chinese population. Previous published data from another Asian population were included in the meta-analysis. RESULT - There were no significant differences in the minor allele frequency and genotype frequency between ET and controls in our Chinese population. However, in the pooled analysis involving 1201 subjects, patients with ET had a higher proportion of GG genotype compared to controls. Logistic regression analysis revealed that G allele increased the risk of ET via a recessive model. In both familial ET and sporadic ET, the G allele increased the risk via a recessive model. CONCLUSION - While we could not demonstrate a significant association of the rs9652490 variant in our own study, pooled analysis of a much larger cohort revealed for the first time that the variant increased the risk in both familial and sporadic forms of ET among Asians, though the effect was stronger in familial ET.
Asunto(s)
Pueblo Asiatico/genética , Temblor Esencial/etnología , Temblor Esencial/genética , Predisposición Genética a la Enfermedad , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Femenino , Pool de Genes , Estudio de Asociación del Genoma Completo , Genotipo , Hospitales de Enseñanza , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Vigilancia de la Población , RiesgoRESUMEN
In order to determine the prevalence of GIGYF2 (Grb10-Interacting GYF Protein 2) variants in the Chinese population and to better understand the association between GIGYF2 and Parkinson's disease (PD), we conducted the genetic screening of GIGYF2 in the Chinese population. Twelve exonic variants were identified in 52 familial PD probands and 56 healthy controls. Non-synonymous point variants (Thr25Ala, Asn457Th and Pro460Th) were analyzed in 510 PD patients and 481 healthy controls of Chinese Han ethnicity. The insertion and deletion variants in Exon 25 (Ins Q 1212, Ins QQ 1217, Del Q 1210, Del Q 1216 and Del PPQ1217_1219) are not related to the onset of familial PD. Our data indicate the GIGYF2 variants are not associated with PD in the mainland Chinese Population.