Delineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population

Contains fulltext : 225115.pdf (publisher's version ) (Open Access)BACKGROUND: Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs. METHODS: We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤ 1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines. RESULTS: Sixty-six patients with pre-biopsy MDC scores of 3-8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n = 3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC. CONCLUSIONS: We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant, was a founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous

Life Cycles in Marine Ornamental Species : Fishes as a Case Study

27 pagesMarine ornamental fish show a great variety of sexual patterns that are the result of specific evolutionary selections and environmental adaptation. Most of the species can be divided into pelagic and demersal spawners. Pelagic spawners usually release gametes in the water column at dusk while demersal spawners have adhesive embryos and parental care. These two modes of reproduction show several differences and specificities, and are fully analyzed in the present chapter. This information is fundamental to the selection of the appropriate species to culturePeer Reviewe

Sex-change and gonadal steroids in sequentially-hermaphroditic teleost fish

Sex-change is an intriguing phenomenon that is common among certain groups of teleost fishes. The process itself has a number of independent origins, although in each case it is initiated and (or) regulated by gonadal steroids. Despite the commercial importance of sex-change technology to fish culturists, our understanding of the relationship between steroids and sex-change is, at best, rudimentary. In this paper I review the current state of knowledge concerning (a) which steroids are involved, (b) how such steroids mediate sex-change, and (c) how steroidogenesis is regulated during gonadal transition. I conclude that the steroidal endocrinology of sex-change is multifarious and species specific – a result which challenges the relative stability of vertebrate endocrine axes, but one which probably reflects the independent evolution of this adaptation