Human CHN1 ELISA Matched Antibody Pair

PURPOSE We describe the clinical phenotype of a Mexican family segregating Duane syndrome as ail reported autosomal-dominant trait linked to chromosome 2q31 (DURS2) and previously to harbor a heterozygous alpha 2-chimaerin missense mutation. METHODS A 5-generation Mexican family was analyzed. Ten affected subjects were available for clinical examination. Participating subjects were tested for visual acuity, ocular alignment by prism cover testing, ocular ductions and versions, and globe retraction. In children, alignment was measured with the Krimsky test in cardinal positions of gaze. RESULTS Ten cases were included, 6 female and 4 male subjects. Five cases presented with bilateral and 5 with unilateral Duane syndrome. The right side was the most commonly affected side on unilateral cases. Five cases exhibited exotropia, 4 esotropia, and 1 hypotropia. Seven patients had severe limitation of abduction and two had moderate limitation. Four patients had mild adduction limitation and 4 had moderate limitation. No additional anomalies such as fourth (trochlear) nerve palsy, blepharoptosis, or dense amblyopia, which have been reported in previous families with Duane syndrome, were observed. All 3 cases that exhibited vertical dysfunction had upgaze limitation. One instance of nonpenetrance was recorded. CONCLUSIONS Considerable intrafamilial clinical variability was observed in this Duane syndrome pedigree that carried a alpha 2-chimaerin mutation. The presence of bilateral involvement and associated vertical movements, which commonly are observed in this and other DURS2 families, could suggest the occurrence of CHN1 mutations as the source of the disease in isolated or familial DURS cases. (J AAPOS 2009-13:245-248)

Short-acting beta agonists (e.g., albuterol) are the most commonly used medications for asthma, a disease that affects over 300 million people in the world. Metabolomic profiling of asthmatics taking b agonists presents a new and promising resource for identifying the molecular determinants of asthma control. The objective is to identify novel genetic and biochemical predictors of asthma control using an integrative "omics'' approach. We generated lipidomic data by liquid chromatography tandem mass spectrometry (LC-MS), using plasma samples from 20 individuals with asthma. The outcome of interest was a binary indicator of asthma control defined by the use of albuterol inhalers in the preceding week. We integrated metabolomic data with genome-wide genotype, gene expression, and methylation data of this cohort to identify genomic and molecular indicators of asthma control. A Conditional Gaussian Bayesian Network (CGBN) was generated using the strongest predictors from each of these analyses. Integrative and metabolic pathway over-representation analyses (ORA) identified enrichment of known biological pathways within the strongest molecular determinants. Of the 64 metabolites measured, 32 had known identities. The CGBN model based on four SNPs (rs9522789, rs7147228, rs2701423, rs759582) and two metabolites-monoHETE_0863 and sphingosine-1-phosphate (S1P) could predict asthma control with an AUC of 95%. Integrative ORA identified 17 significantly enriched pathways related to cellular immune response, interferon signaling, and cytokine-related signaling, for which arachidonic acid, PGE2 and S1P, in addition to six genes (CHN1, PRKCE, GNA12, OASL, OAS1, and IFIT3) appeared to drive the pathway results. Of these predictors, S1P, GNA12, and PRKCE were enriched in the results from integrative and metabolic ORAs. Through an integrative analysis of metabolomic, genomic, and methylation data from a small cohort of asthmatics, we implicate altered metabolic pathways, related to sphingolipid metabolism, in asthma control. These results provide insight into the pathophysiology of asthma control.