Autism is a neurodevelopmental disorder of unknown origin that manifests in early childhood. Autism spectrum disorders (ASDs) refer to a broader group of neurobiological conditions, pervasive developmental disorders. Despite several arguments for a strong genetic contribution, the molecular basis in most cases remains unexplained. Several studies have reported an association between ASDs and mutations in the mitochondrial DNA (mtDNA) molecule. In order to confirm these causative relationship, we screened 21 individuals with idiopathic ASDs for a number of the most common mtDNA mutations. We identified two patients with candidate mutations: m.6852G>A that produces an amino acid change of glycine to serine in the MT-CO1 gene and m.8033A>G (Ile→Val) in the MT-CO2 gene. Overall, these findings support the notion that mitochondrial mutations are associated with ASDs. Additional studies are needed to further define the role of mitochondrial defects in the pathogenesis of autism.
NK cell function is controlled by the cell expression of killer immunoglobulin-like receptors (KIRs) and their ligation with the corresponding HLA ligands. Various malignancies have been associated with certain KIRs surface cell expression and various KIR/HLA ligand combinations. Prior research using case/control study design demonstrates the role of KIR and KIR HLA ligands as genetic factor involved in tumor susceptibility. The objective of this study was to investigate the family-based association of KIRs, HLA class I ligands and KIR/ligand combinations with leukemia diagnosis in families having a leukemia diagnosed child. Sixty-seven families that met the index leukemia case criteria (acute lymphoblastic leukemia, ALL, n = 45; acute myeloid leukemia, AML, n = 13; chronic myeloid leukemia, CML, n = 9; first degree healthy relatives n = 159) were examined. Our study consisted of two phases. In Phase1 case-control study, we primarily compared patients to their healthy siblings to asses if a marker or genotype may be associated with leukemia, excluding the impact of the environment. Phase 2 consisted of a secondary family-based association study. KIR genotyping was performed by PCR-SSP method. KIR HLA ligands were defined by direct method using PCR-SSP method and/or indirect base on high resolution typing of HLA-A, -B, -C alleles. Results of phase 1 showed an increase in the frequency of KIR genotype (with a ratio = 0.57; higher frequency for inhibitory KIRs vs. activating KIRs) among leukemia patients compared to healthy siblings. Results of the phase 2 familial study observed an association between HLA-C1+/BBw4+/ABw4+ haplotype (a mediator of inhibitory signals) and leukemia. Also, we concluded that the absence of HLA-ABw4 alleles was related to leukemia development.
Antiphospholipid syndrome (APS) is an autoimmune disease with multifactorial and polygenic pathogenesis. Recently, the genetic predisposition in APS has been subjected to wide discussion. The aim of this study is to determine the prevalence of DRB1 and DQB1 loci in Bulgarian population of healthy persons and patients with primary (PAPS) and secondary (SAPS) APS. Patients are divided in 5 groups: I-29 patents with systemic lupus erythematosus (SLE) with SAPS, II-35 patients with PAPS, III-32 women with spontaneous abortions without aPL, IV-15 patients with different thrombosis (deep venous thromboses, pulmonary embolism, mesenterial thrombosis, myocardial infarction, stroke) without laboratory data for APS, and V-16 SLE patients without clinical and laboratory data for APS. SAPS patients have more frequently DRB1*03 and DQB1*02 and more rarely DRB1*11 and DQB1*03 in comparison with healthy subjects and patients with PAPS. Patents with PAPS, those with spontaneous abortions and patients with thrombotic events but without antiphospholipid antibodies (aPL) have DRB1*03, DRB1*11, DQB1*02 and DQB1*03 alleles similar to the general population. There are no differences between group I (SLE+APS) and group V (SLE) in DRB1* and DQB1*alleles.