Chromosomal microarray in a highly consanguineous population: diagnostic yield, utility of regions of homozygosity, and novel mutations.

Chromosomal microarray (CMA) has significantly improved diagnosing copy number variations (CNVs). Single nucleotide polymorphism (SNP) arrays confer additional utility in detecting regions of homozygosity (ROH). Investigating ROH for genes associated with recessive disorders for follow-up sequencing can aid in diagnosis. In this study, we performed a retrospective review of clinical and molecular data for 227 individuals from a highly consanguineous population who previously had a CMA. Pathogenic CNVs were identified in 32 (14%) cases; ROH suggesting uniparental disomy (UPD) in three (1%) cases, and an additional 25 (11%) individuals were diagnosed with recessive disorders caused by mutations in ROH candidate genes, thereby increasing the CMA diagnostic yield to 26%. Among the 25 individuals with recessive diseases, 18 had novel mutations in 16 genes (ASPM, SPINK5, QARS, MEGF10, SPATA7, GMPPA, ABCA4, SRD5A2, RPGRIP1L, MET, SLC12A6, ALDH1A3, TNFRSF11A, FLNB, PHGDH, and FKBP10) including five with phenotypic expansion.

Health-related quality of life of adolescents with overweight or obesity in the north of Jordan.

BACKGROUND: Previous studies showed that overweight and obesity in children and adolescents are associated with impaired health-related quality of life (QOL). The objective of this study was to describe health-related QOL among Jordanian adolescents who were overweight or obese. METHODS: This is a cross-sectional study conducted among Jordanian students aged between 13 and 18 years in three educational directorates in Irbid City in the north of Jordan. Using simple random sampling, two male schools and two female schools were selected from the list of each directorate to represent all schools in north of Jordan. In each selected school, all adolescents aged 13-18 years were visited in their classes and were invited to participate in the study. Of the total number of 1561 subjects, 1433 (91.8%) agreed to participate in the study. The short-form 15-item Pediatric Quality of Life Inventory version 4.00 was used to measure health-related QOL among participants. Body mass index (BMI) was calculated and interpreted according to the BMI-for-age growth charts of the Center for Disease Control and Prevention guidelines. RESULTS: This study included 707 boys and 726 girls; 17.6% of participants were overweight and 7.8% were obese. For boys and girls, adolescents who were overweight or obese had significantly lower average scores for psychosocial health summary scale and physical functioning scale. Female gender, age of 16-18 years, fathers' education of high school or less and unemployed fathers (for social functioning and physical functioning) were significantly associated with decreased average scores of all scales and subscales of Pediatric Quality of Life Inventory. CONCLUSIONS: Compared with healthy adolescents, adolescents who were overweight or obese reported significantly lower health-related QOL in all domains. Girls reported greater effect of overweight and obesity on their health-related QOL.

Peroxidases inhibit nitric oxide (NO) dependent bronchodilation: development of a model describing NO-peroxidase interactions.

Recent studies demonstrate that nitric oxide (NO) serves as a physiological substrate for mammalian peroxidases [(2000) J. Biol. Chem. 275, 37524]. We now show that eosinophil peroxidase (EPO) and lactoperoxidase (LPO), peroxidases known to be enriched in airways of asthmatic subjects, function as a catalytic sink for NO, modulating its bioavailability and function. Using NO-selective electrodes and direct spectroscopic and rapid kinetic methods, we examined the interactions of NO with EPO and LPO compounds I and II and ferric forms and compared the results to those reported for myeloperoxidase. A unified kinetic model for NO interactions with intermediates of mammalian peroxidases during steady-state catalysis is presented that accommodates unique features observed with each member of the mammalian peroxidase superfamily. Potential functional consequences of peroxidase-NO interactions in asthma are investigated by utilizing organ chamber studies with tracheal rings. In the presence of pathophysiologically relevant levels of peroxidases and H(2)O(2), NO-dependent bronchodilation of preconstricted tracheal rings was reversibly inhibited. Thus, NO interaction with mammalian peroxidases may serve as a potential mechanism for modulating their catalytic activities, influencing the regulation of local inflammatory and infectious events in vivo.