Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive disorder characterized by hyperactive phagocytes and defects in natural killer cell function. It has been shown previously that mutations in the perforin 1 gene (PRF1) and in UNC13D are associated with FHL2 and FHL3, respectively, indicating genetic heterogeneity. We performed genome-wide homozygosity mapping in a large consanguineous Kurdish kindred with five children affected with FHL. Linkage to a 10 cM region on chromosome 6q24 between D6S1569 and D6S960 defined a novel FHL locus. By screening positional candidate genes, we identified a homozygous deletion of 5 bp in the syntaxin 11 gene (STX11) in this family. We could demonstrate that syntaxin 11 protein was absent in the mononuclear cell fraction of patients with the homozygous 5 bp deletion. In addition to this family, we found homozygous mutations in STX11 in five consanguineous Turkish/Kurdish FHL kindreds including two families with the 5 bp deletion, one family with a large 19.2 kb genomic deletion spanning the entire coding region of STX11 (exon 2) and two families with a nonsense mutation that leads to a premature stop codon in the C-terminal end of the protein. As both STX11 and UNC13D are involved in vesicle trafficking and membrane fusion, we conclude that, besides mutations in perforin 1, defects in the endocytotic or the exocytotic pathway may be a common mechanism in FHL.
Turkish and Kurdish HLA profiles are studied for the first time. The comparative study of their allele frequencies, characteristic haplotypes, genetic distances with other Mediterraneans is complemented by neighbor-joining dendrograms and correspondence analyses. Turks, Kurds, Armenians, Iranians, Jews, Lebanese and other (Eastern and Western) Mediterranean groups seem to share a common ancestry: the older "Mediterranean" substratum. No sign of the postulated Indo-European (Aryan) invasion (1200 B.C.) is detected by our genetic analysis. It is concluded that this invasion, if occurred, had a relatively few invaders in comparison to the already settled populations, i.e. Anatolian Hittite and Hurrian groups (older than 2000 B.C.). These may have given rise to present-day Kurdish, Armenian and Turkish populations.
We have analysed the frequency of killer immunoglobulin-like receptors (KIR) in cohorts of patients from Turkey with acute lymphocyte leukaemia (n = 52), acute myeloid leukaemia (n = 54) and chronic myeloid leukaemia (CML) (n = 52) and compared the results with 154 controls. We also examined the frequencies of human leucocyte antigen (HLA)-C groups, -Bw4, -Bw6 and where appropriate the combination of the KIR gene and its ligand. We found several statistically significant results between the patients and the controls. We proposed a model in CML of protection via KIR2DL2 and/or KIR2DS2 with the presence of the ligand HLA-C1 group and susceptibility via HLA-Bw4 homozygosity (i.e. absence of HLA-Bw6).
The aim of the study was to investigate whether human leukocyte antigen (HLA) allele sharing between partners or the maternal killer immunoglobulin-like receptor (KIR) repertoire is associated with recurrent spontaneous abortion (RSA) and repeated implantation failure after in vitro fertilization (IVF)/embryo transfer. From a total population of 158 RSA couples, 40 couples with repeated implantation failures (IVF) and 81 control couples, reported by five different laboratories, analysis was performed for (a) HLA sharing in 50 RSA, 31 IVF and 31 control couples, (b) DQA1*0505 sharing/homozygosity among partners in 108 RSA, 40 IVF and 36 control couples, and (c) the women's KIR repertoire in 46 RSA, 26 IVF and 36 control wives. RSA couples were divided into alloimmune aborter (RSAallo) and autoimmune aborter (RSAauto). The results oppose to the suggestion that increased HLA sharing per se or a limited maternal KIR repertoire predisposes to RSA or IVF failure. However, the observation of a slightly higher percentage of DQA1*0505 sharing in the RSAauto and the IVF group needs further investigation. The ratio of inhibitory to activating KIR (actKIR) was slightly lower in RSAallo and IVF women (1.9 vs 2.6 in controls), while in a high percentage of these women, the standard receptors of the KIR A haplotype were combined with actKIR/s of the haplotype B (66.6% and 45.4% vs 20% and 15.3% in RSAauto and control groups). This may suggest a possible involvement of actKIRs in embryo implantation and the maintenance of pregnancy and also requires further investigation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.