A Post‐Hoc Comparison of the Utility of Sanger Sequencing and Exome Sequencing for the Diagnosis of Heterogeneous Diseases

The advent of massive parallel sequencing is rapidly changing the strategies employed for the genetic diagnosis and research of rare diseases that involve a large number of genes. So far it is not clear whether these approaches perform significantly better than conventional single gene testing as requested by clinicians. The current yield of this traditional diagnostic approach depends on a complex of factors that include gene‐specific phenotype traits, and the relative frequency of the involvement of specific genes. To gauge the impact of the paradigm shift that is occurring in molecular diagnostics, we assessed traditional Sanger‐based sequencing (in 2011) and exome sequencing followed by targeted bioinformatics analysis (in 2012) for five different conditions that are highly heterogeneous, and for which our center provides molecular diagnosis. We find that exome sequencing has a much higher diagnostic yield than Sanger sequencing for deafness, blindness, mitochondrial disease, and movement disorders. For microsatellite‐stable colorectal cancer, this was low under both strategies. Even if all genes that could have been ordered by physicians had been tested, the larger number of genes captured by the exome would still have led to a clearly superior diagnostic yield at a fraction of the cost.     

Pancreatic ductal adenocarcinoma and acinar cells: a matter of differentiation and development?

Pancreatic ductal adenocarcinoma (PDAC) has long been considered to arise from pancreatic ducts on the basis of its morphology, the occurrence of dysplasia in putative preneoplastic ductal lesions, and the absence of acinar dysplasia in the pancreas of patients with PDAC. However, evidence gathered through both in vitro studies and--more importantly--genetic mouse models of PDAC shows that ductal-type tumours can arise from acinar cells. These findings raise new important questions related to PDAC pathophysiology and call for in-depth studies of acinar cell differentiation in order to better understand PDAC biology. The authors review these issues and discuss how the novel findings should impact on future work aiming at early diagnosis and improved outcome of patients with PDAC.     

Emotion differentiation in autism spectrum disorder

Autism spectrum disorder (ASD) is commonly associated with reduced ability to recognize emotions in others. It is less clear however, whether ASD is also associated with impaired knowledge of one's own emotions. In the current study we present a first examination of how much knowledge individuals with ASD have about their emotions by investigating their ability to differentiate between emotions. Across two lab tasks that measured to what extent and how people differentiate between their own feeling states and semantic emotion terms, results showed that ASD individuals differentiated less than typically developing individuals. Yet, both groups of participants similarly categorized emotions according to previously established theoretical categories. These findings indicate that while both give similar meaning to emotions, individuals with ASD make less subtle distinctions between emotions. With low levels of emotion differentiation being linked to reduced well-being, these findings may help to better understand the high prevalence of internalizing problems associated with ASD.