BackgroundHigh throughput sequencing technologies have revolutionized the identification of mutations responsible for genetic diseases such as hypertrophic cardiomyopathy (HCM). However, approximately 50% of individuals with a clinical diagnosis of HCM have no causal mutation identified. This may be due to the presence of pathogenic mutations located deep within the introns, which are not detected by conventional sequencing analysis restricted to exons and exon-intron boundaries.ObjectiveThe aim of this study was to develop a whole-gene sequencing strategy to prioritize deep intronic variants that may play a role in HCM pathogenesis.Methods and resultsThe full genomic DNA sequence of 26 genes previously associated with HCM was analysed in 16 unrelated patients. We identified likely pathogenic deep intronic variants in VCL, PRKAG2 and TTN genes. These variants, which are predicted to act through disruption of either splicing or transcription factor binding sites, are 3-fold more frequent in our cohort of probands than in normal European populations. Moreover, we found a patient that is compound heterozygous for a splice site mutation in MYBPC3 and the deep intronic VCL variant. Analysis of family members revealed that carriers of the MYBPC3 mutation alone do not manifest the disease, while family members that are compound heterozygous are clinically affected.ConclusionThis study provides a framework for scrutinizing variation along the complete intronic sequence of HCM-associated genes and prioritizing candidates for mechanistic and functional analysis. Our data suggest that deep intronic variation contributes to HCM phenotype.

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The meagre Argyrosomus regius, one of the largest sciaenidae in the world, is a valuable resource for fisheries and aquaculture. Despite its socioeconomic relevance, knowledge about population dynamics and wild stocks is still scarce, and conservation risks are associated with overexploitation. Two genetic distinct groups, one in the North Atlantic Ocean and one in the eastern Mediterranean Sea, were identified by previous studies. However, little is known about the genetic structure of the Atlantic group, where four important spawning areas have been identified. To assess if each spawning area is an independent breeding unit, the genetic diversity, populational structure, and demographic history of A. regius along the North–East and Eastern Central Atlantic coast were analyzed, using 15 microsatellite loci. Results corroborate the hypothesis tested, suggesting four genetic groups: a first group encompassing individuals from the Gironde spawning area, a second group encompassing individuals from the Tagus spawning area, a third group corresponding to individuals captured in the Algarve region, and a forth group gathering individuals from Morocco and Mauritania. This study reveals the need for specific fisheries management plans considering genetic structure information, and highlights the need for international cooperation.

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