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Abstract Background Bi-allelic mutations in FAM20C gene are known to cause a rare genetic disorder- Raine syndrome (RS). The FAM20C protein binds calcium and phosphorylates proteins involved in biomineralization of bones and teeth. RS is recognized as an osteosclerotic bone dysplasia. It is characterized by distinctive facial features, generalized osteosclerosis and respiratory insufficiency along with periosteal bone formation. RS is typically described as being an aggressive skeletal dysplasia with death in the neonatal period or early infancy. However, in the recent past an increasing number of individuals having an extended life span along with a highly heterogeneous phenotype has led to classifying RS into short and extended lifespan categories. Case presentation We report a case of RS with antenatal fractures, facial dysmorphism and osteosclerosis without significant respiratory manifestations. The child has a relatively extended lifespan, whereby she died at 17-months of age. Clinical exome sequencing revealed a previously known, homozygous, nonsense variant c.1680C > A (p.Cys560Ter) in exon 10 of FAM20C. Whilst the variant was initially classified as a variant of uncertain significance (VUS), through the latest release of gnomAD and GTEx data, this was subsequently re-classified as likely pathogenic. Furthermore, segregation analysis showed both parents to be carriers. In contrast, a previously reported case with the same variant had polyhydramnios, complex facial abnormalities and bright echogenic brain parenchyma with oval shaped skull and anterior flattening at 26 weeks of gestation. Conclusion The variant identified has been previously reported as a VUS. The present case provides further evidence towards the pathogenicity of the variant. A plausible genotype-phenotype correlation based on the location of the variant has been verified, wherein the position of a nonsense variant in the terminal exon of FAM20C gene, could have had a partial effect on the protein function, thereby resulting in a relatively milder phenotype and extended lifespan. Furthermore, the vast phenotypic variation on clinical comparison current case and a previously reported case, despite having the same genotype, could suggest an oligogenic effect and/ or environmental influence.

Background: Bi-allelic mutations in FAM20C gene are known to cause a rare genetic disorder- Raine syndrome (RS). The FAM20C protein binds calcium and phosphorylates proteins involved in biomineralization of bones and teeth. RS is recognized as an osteosclerotic bone dysplasia. It is characterized by distinctive facial features, generalized osteosclerosis and respiratory insufficiency along with periosteal bone formation. RS is typically described as being an aggressive skeletal dysplasia with death in the neonatal period or early infancy. However, in the recent past an increasing number of individuals having an extended life span along with a highly heterogeneous phenotype has led to classifying RS into short and extended lifespan categories.Case Presentation: We report a case of RS with antenatal fractures, facial dysmorphism and osteosclerosis without significant respiratory manifestations. The child has a relatively extended lifespan, whereby she died at 17-months of age. Clinical exome sequencing revealed a previously known, homozygous, nonsense variant c.1680C > A (p.Cys560Ter) in exon 10 of FAM20C. Whilst the variant was initially classified as a variant of uncertain significance (VUS), through the latest release of gnomAD and GTEx data, this was subsequently re-classified as likely pathogenic. Furthermore, segregation analysis showed both parents to be carriers. In contrast, a previously reported case with the same variant had polyhydramnios, complex facial abnormalities and bright echogenic brain parenchyma with oval shaped skull and anterior flattening at 26 weeks of gestation.Conclusion: The variant identified has been previously reported as a VUS. The present case provides further evidence towards the pathogenicity of the variant. A plausible genotype-phenotype correlation based on the location of the variant has been verified, wherein the position of a nonsense variant in the terminal exon of FAM20C gene, could have had a partial effect on the protein function, thereby resulting in a relatively milder phenotype and extended lifespan. Furthermore, the vast phenotypic variation on clinical comparison current case and a previously reported case, despite having the same genotype, could suggest an oligogenic effect and/ or environmental influence. [ABSTRACT FROM AUTHOR]

The reversible posttranslational O-GlcNAc modification of serine or threonine residues of intracellular proteins is involved in many cellular events from signaling cascades to epigenetic and transcriptional regulation. O-GlcNAcylation is a conserved nutrient-dependent process involving two enzymes, with O-GlcNAc transferase (OGT) adding O-GlcNAc and with O-GlcNAcase (OGA) removing it in a manner that’s protein- and context-dependent. O-GlcNAcylation is essential for epigenetic regulation of gene expression through its action on Polycomb and Trithorax and COMPASS complexes. However, the important role of O-GlcNAc in adult life and health span has been largely unexplored, mainly due the lack of available model systems. Cataloging the O-GlcNAc proteome has proven useful in understanding the biology of this modification in vivo. In this study, we leveraged a recently developed oga knockout fly mutant to identify the O-GlcNAcylated proteins in adult Drosophilamelanogaster. The adult O-GlcNAc proteome revealed many proteins related to cell and organismal growth, development, differentiation, and epigenetics. We identified many O-GlcNAcylated proteins that play a role in increased growth and decreased longevity, including HCF, SIN3A, LOLA, KISMET, ATX2, SHOT, and FOXO. Interestingly, oga mutant flies are larger and have a shorter life span compared to wild type flies, suggesting increased O-GlcNAc results in increased growth. Our results suggest that O-GlcNAc alters the function of many proteins related to transcription, epigenetic modification and signaling pathways that regulate growth rate and longevity. Therefore, our findings highlight the importance of O-GlcNAc in growth and life span in adult Drosophila.

The majority of coral reef goby species are short-lived, with some highly abundant species living less than 100 d. To understand the role and consequences of this extreme life history in shaping coral reef fish populations, we quantitatively documented the structure of small reef fish populations over a 26-month period (>14 short-lived fish generations) at an inshore reef on the Great Barrier Reef, Australia. Most species with life spans >1 yr, such as pomacentrids, exhibited a peak in recruitment during the austral summer, driving seasonal changes in the small fish community composition. In contrast, there were no clear changes in goby community composition, despite the abundance of short-lived, high turnover species. Species of Eviota, the most abundant gobiid genus observed, showed remarkably similar demographic profiles year-round, with consistent densities of adults as well as recently recruited juveniles. Our results demonstrate ongoing recruitment of these small cryptic fishes, which appears to compensate for an exceptionally short life span on the reef. Our results suggest that gobiid populations are able to overcome demographic limitations, and by maintaining reproduction, larval survival and recruitment throughout the year, they may avoid population bottlenecks. These findings also underline the potential trophodynamic importance of these small species; because of this constant turnover, Eviota species and other short-lived fishes may be particularly valuable contributors to the flow of energy on coral reefs, underpinning the year-round trophic structure. [ABSTRACT FROM AUTHOR]

The life-history traits of two species of pipefish (Syngnathidae) from seagrass meadows in New South Wales, Australia, were examined to understand whether they enhance resilience to habitat degradation. The spotted pipefish Stigmatopora argus and wide-bodied pipefish Stigmatopora nigra exhibit some of the shortest life spans known for vertebrates (longevity up to 150 days) and rapid maturity (male S. argus 35 days after hatching ( DAH) and male S. nigra at 16-19 DAH), key characteristics of opportunistic species. Growth rates of both species were extremely rapid (up to 2 mm day−1), with seasonal and sex differences in growth rate. It is argued that short life spans and high growth rates may be advantageous for these species, which inhabit one of the most threatened marine ecosystems on earth. [ABSTRACT FROM AUTHOR]

• The msh1 gene is responsible for the nd (natural death) mutation in Neurospora. • Phenotype of very early cease of hyphal growth was caused by knocking out of the msh1 gene. • In the nd and msh1KO strains, instability of mtDNA induces mitochondrial dysfunction and acceleration of aging. • MSH1 protein localizes in mitochondria and may suppress the unexpected intra-molecular recombination of mtDNA. Wild-type filamentous fungus Neurospora crassa continues to grow its hyphae for a very lengthy period of time (>2 years), whereas mutations at the natural death (nd) locus shorten life span (approximately 20 days). By positional cloning based on heat augmented mutagen sensitivity of the nd strain, we identified a nonsense mutation in the msh1 gene , an eukaryotic homolog of bacterial MutS, and this mutation resulted in encoding non-functional polypeptide. By tagging with GFP, subcellular localization of the MSH1 protein in the mitochondria was observed, and knock out of the msh1 gene caused severe growth deficiency accompanying mitochondrial DNA (mtDNA) aberrations such as large-scale mtDNA deletions and rearrangements as seen in the nd strain. These results suggested that MSH1 may maintain mtDNA integrity. Thus, loss of function compromises mtDNA, leading to the acceleration of cellular aging. [ABSTRACT FROM AUTHOR]