Development of an e-learning portal for pediatric endocrinology: educational considerations

Background: Global accessibility and dissemination of developments in pediatric endocrinology prompted to examine how to develop an educational interactive e-SPE web portal. Methods: A systematic approach was used to identify the relevant aspects of accessibility and dissemination. An orientation at the big idea was made, executed by an analysis of the needs of student and teacher pediatric endocrinologists, a definition of the learning objectives, a research in educational literature and an exploration of ICT design specifications. Results: The intensive collaboration between medical, educational and information technology disciplines resulted in a portal design. The portal meets requirements of adult learning, stresses interaction between partners in learning and offers direct feedback during the learning process. The portal supports the development of not only knowledge but also competences both at junior and advanced levels. Conclusion: When the e-SPE portal is completed, the options for summative assessment will be examined as a medium for international certification in conjunction with local and national requirements (http://espe.elearning.nl). Copyrigh

The Results of CHD7 Analysis in Clinically Well-Characterized Patients with Kallmann Syndrome

Item does not contain fulltextCONTEXT: Kallmann syndrome (KS) and CHARGE syndrome are rare heritable disorders in which anosmia and hypogonadotropic hypogonadism co-occur. KS is genetically heterogeneous, and there are at least eight genes involved in its pathogenesis, whereas CHARGE syndrome is caused by autosomal dominant mutations in only one gene, the CHD7 gene. Two independent studies showed that CHD7 mutations can also be found in a minority of KS patients. OBJECTIVE: We aimed to investigate whether CHD7 mutations can give rise to isolated KS or whether additional features of CHARGE syndrome always occur. DESIGN: We performed CHD7 analysis in a cohort of 36 clinically well-characterized Dutch patients with KS but without mutations in KAL1 and with known status for the KS genes with incomplete penetrance, FGFR1, PROK2, PROKR2, and FGF8. RESULTS: We identified three heterozygous CHD7 mutations. The CHD7-positive patients were carefully reexamined and were all found to have additional features of CHARGE syndrome. CONCLUSION: The yield of CHD7 analysis in patients with isolated KS seems very low but increases when additional CHARGE features are present. Therefore, we recommend performing CHD7 analysis in KS patients who have at least two additional CHARGE features or semicircular canal anomalies. Identifying a CHD7 mutation has important clinical implications for the surveillance and genetic counseling of patients

Genome-wide compound heterozygote analysis highlights alleles associated with adult height in Europeans

Adult height is the most widely genetically studied common trait in humans; however, the trait variance explainable by currently known height-associated single nucleotide polymorphisms (SNPs) identified from the previous genome-wide association studies (GWAS) is yet far from complete given the high heritability of this complex trait. To exam if compound heterozygotes (CH) may explain extra height variance, we conducted a genome-wide analysis to screen for CH in association with adult height in 10,631 Dutch Europeans enriched with extremely tall people, using our recently developed method implemented in the software package CollapsABEL. The analysis identified six regions (3q23, 5q35.1, 6p21.31, 6p21.33, 7q21.2, and 9p24.3), where multiple pairs of SNPs as CH showed genome-wide significant association with height (P < 1.67 × 10−10). Of those, 9p24.3 represents a novel region influencing adult height, whereas the others have been highlighted in the previous GWAS on height based on analysis of individual SNPs. A replication analysis in 4080 Australians of European ancestry confirmed the significant CH-like association at 9p24.3 (P < 0.05). Together, the collapsed genotypes at these six loci explained 2.51% of the height variance (after adjusting for sex and age), compared with 3.23% explained by the 14 top-associated SNPs at 14 loci identified by traditional GWAS in the same data set (P < 5 × 10−8). Overall, our study empirically demonstrates that CH plays an important role in adult height and may explain a proportion of its “missing heritability”. Moreover, our findings raise promising expectations for other highly polygenic complex traits to explain missing heritability identifiable through CH-like associations