RESUMO
Cockayne syndrome (CS) is one the rare DNA-repair deficiency disorders with autosomal recessive inheritance. Failure to thrive and microcephaly are the major criteria of diagnosis. Owing to genetic heterogeneity of CS, whole exome sequencing is promising way to determine the genetic basis of the disease. Here, we present c.1053delT in ERCC8 gene in an Iranian family with symptom of CS using whole exome sequencing. The deletion was novel and was not previously reported elsewhere.
Assuntos
Síndrome de Cockayne/genética , Enzimas Reparadoras do DNA/genética , Deleção de Sequência , Fatores de Transcrição/genética , Sequência de Aminoácidos , Criança , Feminino , Humanos , Irã (Geográfico) , Masculino , Linhagem , Sequenciamento do ExomaRESUMO
Multiple sclerosis (MS) is a common autoimmune disorder of the central nervous system. Recent studies have shown that the HLA-DRB1 and DQB1 alleles are associated with MS susceptibility and severity. However, this is controversial in different population studies. In the present study, the roles of HLA-DRB1 and DQB1 alleles and the amino acids were investigated on disease risk and severity in 120 Iranian patients with MS and 120 controls. Our findings indicate that the DRB1*1501 allele (OR = 3.203 P = 0.001), the DRB1*1501-DQB1*0602 haplotype (OR = 7.792 P = 0.003) and the DRB1*1501/0701- genotype (OR = 3.320 P = 0.006) and amino acid Leu26 (OR = 1.645 P = 0.005) and Phe9 (OR = 1.893 P = 0.009) on the DQß1 chain are significantly associated with MS susceptibility. DRB1*1001 was the only allele that had a protective effect against MS (P = 0.0004). We also found that the DQB1*0303 allele was significantly associated with disease severity (mean Multiple Sclerosis Severity Score difference = 1.979, P = 0.002). However, protective effect of the DRB1*1001 against MS and also association of DQB1*0303 allele with MS severity need to be confirmed by larger sample size.
Assuntos
Alelos , Heterogeneidade Genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Esclerose Múltipla/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Irã (Geográfico)/epidemiologia , Leucina/metabolismo , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Razão de Chances , Fatores de Risco , Índice de Gravidade de Doença , População Branca/genética , Adulto JovemRESUMO
BACKGROUND/AIMS: Alzheimer disease (AD) is a complex and genetically heterogeneous disorder, and certain genes such as PS2 and APOE4 contribute to the development of AD. Due to its heterogeneity, AD-predisposing genes could vary in different populations. Moreover, not all AD patients will respond to the same therapy. We specifically investigated the effect ofrivastigmine (Exelon) on PS2 and APOE genes in Iranian AD patients. METHODS: A total of 100 AD patients, 67 patients with sporadic AD (SAD) and 33 patients with familial AD (FAD), receiving rivastigmine therapy and 100 healthy controls were studied. PCR-RFLP was used for genotyping of PS2 and APOE. RESULTS: We found a positive association between the PS2 -A allele and SAD patients (p(c) = 0.01), and the PS2 +A/-A genotype was significantly more frequent in SAD than FAD patients (p(c) = 0.009). The APOE4 allele was associated with total AD, SAD and FAD (p(c) = 0.000002). Patients with the PS2 +A/-A genotype and bigenic genotypes of +A/-A·∊3/∊3 and +A/-A·∊3/∊4 were the best responders to Exelon therapy, and those with the PS2 +A/+A and APOE ∊3/∊4 genotypes were the worst responders. CONCLUSION: Our findings suggest that the PS2 and APOE4 alleles and genotypes affect both AD risk and response to rivastigmine therapy.