Combined Military Hospital

About: Combined Military Hospital is a healthcare organization based out in Rawalpindi, Pakistan. It is known for research contribution in the topics: Population & Outpatient clinic. The organization has 2129 authors who have published 1619 publications receiving 7882 citations.

Identifying Autism Loci and Genes by Tracing Recent Shared Ancestry

Abstract: To find inherited causes of autism-spectrum disorders, we studied families in which parents share ancestors, enhancing the role of inherited factors. We mapped several loci, some containing large, inherited, homozygous deletions that are likely mutations. The largest deletions implicated genes, including PCDH10 (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58), whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning. A subset of genes, including NHE9 (Na+/H+ exchanger 9), showed additional potential mutations in patients with unrelated parents. Our findings highlight the utility of “homozygosity mapping” in heterogeneous disorders like autism but also suggest that defective regulation of gene expression after neural activity may be a mechanism common to seemingly diverse autism mutations.

A genome-wide linkage and association scan reveals novel loci for autism

Abstract: Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.

Paroxysmal nocturnal hemoglobinuria.

Abstract: Paroxysmal Nocturnal Hemoglobinuria (PNH) literally means to have episodes of hemoglobin in the urine during the night. It is a Coomb's negative rare hemolytic disorder characterized by non-malignant clonal expansion of haemopoietic stem cells due to acquired genetic mutations. A 30 years old male patient presented with 5 years history of transfusion dependent anemia with intermittent episodes of passing dark colored urine in the morning. Blood complete picture showed decreased hemoglobin and reticulocytosis upto 30%. Coomb's test was negative with unconjugated hyperbilirubinemia and markedly raised serum LDH. Urine analysis showed marked hemosiderinuria and flow cytometry revealed 60% RBCs deficient for CD-59, confirming the diagnosis of paroxysmal nocturnal hemoglobinuria. The management of the patient depends on whether anemia is due to hemolysis or as consequence of impaired erythropoiesis. Corticosteroids at a dose of 0.25-1 mg/kg/day was selected as it is amongst the various treatment options in patients with predominant hemolysis.