Induction of phytoextraction, phytoprotection and growth promotion activities in Lupinus albus under mercury abiotic stress conditions by Peribacillus frigoritolerans subsp., mercuritolerans subsp. nov.

Strain SAICEUPBMT was isolated from soils of Almadén (Ciudad Real, Spain), subjected to a high mercury concentration. SAICEUPBMT significantly increased aerial plant weight, aerial plant length and the development of secondary roots under mercury stress; increased twice the absorption of mercury by the plant, while favoring its development in terms of biomass. Similarly, plants inoculated with SAICEUPBMT and grown in soils contaminated with mercury, express a lower activity of antioxidant enzymes; catalase enzymes (CAT), superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR) for defense against ROS (reactive oxygen species). Whole genome analysis showed that ANI (95. 96 %), dDDH (72.9 %), AAI (93.3 %) and TETRA (0.99) values were on the thresholds established for differentiation a subspecies. The fatty acids analysis related the strain with the Peribacillus frigoritolerans species. And the synapomorphic analysis reveals a common ancestor with analysis related the strain with the Peribacillus frigoritolerans species. Results from genomic analysis together with differences in phenotypic features and chemotaxonomic analysis support the proposal of strain SAICEUPBMT as the type strain of a novel subspecies for which the name Peribacillus frigoritolerans subps. mercuritolerans sp. nov is proposed. The absence of virulence genes and transmissible resistance mechanisms reveals its safety for agronomic uses, under mercury stress conditions. The ability of Peribacillus frigoritolerans subsp. mercuritolerans subsp. nov to improve plant development was tested in a Lupinus albus model, demonstrating a great potential for plant phytoprotection against mercury stress.

Positioning of enhanced monofocal intraocular lenses between conventional monofocal and extended depth of focus lenses: a scoping review.

BACKGROUND: New intraocular lenses (IOLs) have emerged since the originally coined monofocal and multifocal IOLs. The extended depth of focus (EDoF) and enhanced monofocal IOLs (mono-EDoF) that have appeared in the last decade have caused some confusion in their classification. The aim of this review was to summarize the outcomes provided by mono-EDOF IOLs and to determine which of the endpoints, described by the American National Standard (ANSI) for EDoF IOLs, are fulfilled. METHODS: The MEDLINE, EMBASE, and WEB OF SCIENCE databases were searched. Two independent reviewers screened the studies for inclusion and data extraction. The search strategy was limited to studies published between 2020 and 2022, but not by language. The results are presented as a narrative summary accompanied by tables, in alignment with the objectives of this scoping review. Compliance with the endpoints for clinical outcomes described in the American National Standard Z80.35-2018 (ANSI) for EDoF lenses was checked and additional endpoints were defined. RESULTS: Two systematic reviews, 13 laboratory, 21 clinical, and two mixed studies were included. Tecnis Eyhance was the mono-EDOF with the highest volume of evidence to date. Although laboratory studies included other IOLs, clinical evidence for them is still scarce, with only one study of IsoPure compared to a standard monofocal IOL. Evidence in comparison to EDoF lenses is also scarce, even for Tecnis Eyhance, with only three studies including this lens in comparison to an EDoF lens. After evaluation of the ANSI criteria, agreement was found in the failure for the increase in depth of field equal to or greater than 0.5 D for a visual acuity (VA) level of 0.2 logMAR and none of the studies supported that the median monocular VA at intermediate distance was at least 0.2 logMAR. CONCLUSIONS: Additional clinical evidence is required for other mono-EDOF IOLs beyond Tecnis Eyhance. Until the arrival of a standard classification, mono-EDOF should be better still classified as monofocal because the ANSI standards were not fully met.

Descemet membrane endothelial keratoplasty combined with presbyopia-correcting and toric intraocular lenses - a narrative review.

Fuchs endothelial corneal dystrophy (FECD) is the leading indication for EK and may coexist with cataract and presbyopia. Notably, the outcomes of phacoemulsification in FECD patients are not as favorable as those in eyes without this condition. Historically, only monofocal intraocular lenses (IOLs) were recommended for these patients. However, recent reports have described the implantation of Premium-IOLs (such as Multifocal IOLs, Enhanced Depth of Focus IOLs, and Toric IOLs) in FECD eyes undergoing cataract surgery and Descemet membrane endothelial keratoplasty (DMEK). While the results are encouraging, they are not as optimal as those from unoperated eyes, especially when comparing simultaneous procedures to sequential ones. It's advised to perform the DMEK first to improve the accuracy of IOL calculations. Still, even successfully operated eyes may experience secondary graft failure or graft rejection after DMEK. The success rate of a secondary DMEK is typically lower than that of the initial procedure. Furthermore, if the postoperative thickness after DMEK is less than anticipated, laser enhancements might not be an option. There's a pressing need for more controlled and randomized clinical trials to ascertain the safety and effectiveness of Premium-IOLs for FECD eyes. This narrative review aims to collate evidence on the use of Premium IOL technologies in eyes receiving EK and to underscore key points for surgeons performing EK combined with cataract surgery.

Managing low corneal astigmatism in patients with presbyopia correcting intraocular lenses: a narrative review.

Cataract surgery has become a refractive procedure in which emmetropia is the goal, with the implantation of extended depth-of-focus or multifocal intraocular lenses (IOLs) being the commonly selected option to restore vision beyond the far distance. The selection criteria for implanting these lenses can differ from those for monofocal IOLs and even between technologies, as eye characteristics can affect postoperative visual performance. Corneal astigmatism is an eye characteristic that can affect visual performance differently, depending on the implanted IOL. The magnitude of corneal astigmatism, the tolerance of the IOL to this astigmatism, economic aspects, comorbidities, and the efficacy of astigmatism treatment are factors that can make surgeons' doubt as to what astigmatism treatment should be applied to each patient. This review aims to summarize the current evidence related to low astigmatism tolerance in presbyopia-correcting lenses, the efficacy achieved through corneal incisions, and their comparison with the implantation of toric IOLs.

Bioremediation of environments contaminated with mercury. Present and perspectives.

Mercury is a highly toxic heavy metal whose emission sources can be both natural and the result of anthropic activity. Its polluting action on soils, and its ability to spread through the atmosphere and aquatic environments, constitutes a threat to human and environmental health; both for its bioaccumulation capacity and for biomagnification through the trophic chain. For this reason, there is a growing scientific and social interest in the reduction of this heavy metal in ecosystems. Bioremediation based on the use of microorganisms and/or plants is postulated as a sustainable alternative to traditional physicochemical methods. The main strategies used for this purpose (individually or in combination) are the volatilization of the contaminant, biosorption, phytoextraction and phytoremediation. All these tools are based on taking advantage of the natural and evolutionary capacity that different organisms have developed to adapt to the presence of various pollutants in the environment. Based on the consulted bibliography, these bioremediation methodologies focus on the use of microorganisms (freely or associated with plants) have been successfully applied in different ecosystems, postulating themselves as a respectful alternative for the future for the recovery of degraded environments. For these reasons there is a growing interest in the scientific community to design and use new techniques in a "One Health" context, which allow interpreting the positive impact of bioremediation. In this sense, the universalization of Omics techniques has allowed to abound in the knowledge of new bacterial taxa, and their biotechnological application. This study pretends to cover the present knowledge about mercury bioremediation techniques. In the same way, some new techniques and perspectives are presented in order to expand the frontiers of future research.

Molecular Fingerprint of BMD Patients Lacking a Portion in the Rod Domain of Dystrophin.

BMD is characterized by a marked heterogeneity of gene mutations resulting in many abnormal dystrophin proteins with different expression and residual functions. The smaller dystrophin molecules lacking a portion around exon 48 of the rod domain, named the D8 region, are related to milder phenotypes. The study aimed to determine which proteins might contribute to preserving muscle function in these patients. Patients were subdivided, based on the absence or presence of deletions in the D8 region, into two groups, BMD1 and BMD2. Muscle extracts were analyzed by 2-D DIGE, label-free LC-ESI-MS/MS, and Ingenuity pathway analysis (IPA). Increased levels of proteins typical of fast fibers and of proteins involved in the sarcomere reorganization characterize BMD2. IPA of proteomics datasets indicated in BMD2 prevalence of glycolysis and gluconeogenesis and a correct flux through the TCA cycle enabling them to maintain both metabolism and epithelial adherens junction. A 2-D DIGE analysis revealed an increase of acetylated proteoforms of moonlighting proteins aldolase, enolase, and glyceraldehyde-3-phosphate dehydrogenase that can target the nucleus promoting stem cell recruitment and muscle regeneration. In BMD2, immunoblotting indicated higher levels of myogenin and lower levels of PAX7 and SIRT1/2 associated with a set of proteins identified by proteomics as involved in muscle homeostasis maintenance.

Targeting HDAC8 to ameliorate skeletal muscle differentiation in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) causes progressive skeletal muscle degeneration and currently there are few therapeutic options. The identification of new drug targets and their validation in model systems of DMD could be a promising approach to make progress in finding new treatments for this lethal disease. Histone deacetylases (HDACs) play key roles in myogenesis and the therapeutic approach targeting HDACs in DMD is in an advanced phase of clinical trial. Here, we show that the expression of HDAC8, one of the members of the HDAC family, is increased in DMD patients and dystrophic zebrafish. The selective inhibition of HDAC8 with the PCI-34051 inhibitor rescues skeletal muscle defects, similarly to the treatment with the pan-HDAC inhibitor Givinostat. Through acetylation profile of zebrafish with HDAC8 dysregulation, we identified new HDAC8 targets involved in cytoskeleton organization such as tubulin that, when acetylated, is a marker of stable microtubules. Our work provides evidence of HDAC8 overexpression in DMD patients and zebrafish and supports its specific inhibition as a new valuable therapeutic approach in the treatment of this pathology.

Muscle Proteomic Profile before and after Enzyme Replacement Therapy in Late-Onset Pompe Disease.

Mutations in the acidic alpha-glucosidase (GAA) coding gene cause Pompe disease. Late-onset Pompe disease (LOPD) is characterized by progressive proximal and axial muscle weakness and atrophy, causing respiratory failure. Enzyme replacement therapy (ERT), based on recombinant human GAA infusions, is the only available treatment; however, the efficacy of ERT is variable. Here we address the question whether proteins at variance in LOPD muscle of patients before and after 1 year of ERT, compared withhealthy age-matched subjects (CTR), reveal a specific signature. Proteins extracted from skeletal muscle of LOPD patients and CTR were analyzed by combining gel based (two-dimensional difference gel electrophoresis) and label-free (liquid chromatography-mass spectrometry) proteomic approaches, and ingenuity pathway analysis. Upstream regulators targeting autophagy and lysosomal tethering were assessed by immunoblotting. 178 proteins were changed in abundance in LOPD patients, 47 of them recovered normal level after ERT. Defects in oxidative metabolism, muscle contractile protein regulation, cytoskeletal rearrangement, and membrane reorganization persisted. Metabolic changes, ER stress and UPR (unfolded protein response) contribute to muscle proteostasis dysregulation with active membrane remodeling (high levels of LC3BII/LC3BI) and accumulation of p62, suggesting imbalance in the autophagic process. Active lysosome biogenesis characterizes both LOPD PRE and POST, unparalleled by molecules involved in lysosome tethering (VAMP8, SNAP29, STX17, and GORASP2) and BNIP3. In conclusion this study reveals a specific signature that suggests ERT prolongation and molecular targets to ameliorate patient's outcome.

Mutations in INPP5K Cause a Form of Congenital Muscular Dystrophy Overlapping Marinesco-Sjögren Syndrome and Dystroglycanopathy.

Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjögren syndrome. Whole-exome sequencing revealed homozygous missense and compound heterozygous mutations in INPP5K in the affected members of each family. INPP5K encodes the inositol polyphosphate-5-phosphatase K, also known as SKIP (skeletal muscle and kidney enriched inositol phosphatase), which is highly expressed in the brain and muscle. INPP5K localizes to both the endoplasmic reticulum and to actin ruffles in the cytoplasm. It has been shown to regulate myoblast differentiation and has also been implicated in protein processing through its interaction with the ER chaperone HSPA5/BiP. We show that morpholino-mediated inpp5k loss of function in the zebrafish results in shortened body axis, microphthalmia with disorganized lens, microcephaly, reduced touch-evoked motility, and highly disorganized myofibers. Altogether these data demonstrate that mutations in INPP5K cause a congenital muscular dystrophy syndrome with short stature, cataracts, and intellectual disability.

Aging-associated genes and let-7 microRNAs: a contribution to myogenic program dysregulation in oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease caused by an abnormal (GCN) triplet expansion within the polyadenylate-binding protein nuclear 1 gene and consequent mRNA processing impairment and myogenic defects. Because a reduced cell proliferation potential and the consequent regeneration failure of aging muscle have been shown to be governed by lethal-7 (let-7) microRNA-mediated mechanisms, in the present study, we evaluated the role of let-7 in the pathogenesis of OPMD. By a multidisciplinary approach, including confocal microscopy, Western blot, and quantitative PCR analyses on muscle biopsies from patients and unaffected individuals, we found a significant increase in let-7 expression in OPMD muscles associated with an unusual high percentage of paired box 7-positive satellite cells. Furthermore, IL-6, a cytokine involved in the regulation of satellite cell proliferation and differentiation and a potential target of let-7, was found strongly down-regulated in OPMD compared with control muscles. The decrease in IL-6 transcript levels and protein content was also confirmed in vitro during differentiation of patients' and controls' muscle cells. Overall, our data suggest a key role of let-7 in the regeneration and degeneration process in OPMD muscle and pointed to IL-6 as a potential target molecule for new therapeutic approaches for this disorder.-Cappelletti, C., Galbardi, B., Bruttini, M., Salerno, F., Canioni, E., Pasanisi, M. B., Rodolico, C., Brizzi, T., Mora, M., Renieri, A., Maggi, L., Bernasconi, P., Mantegazza, R. Aging-associated genes and let-7 microRNAs: a contribution to myogenic program dysregulation in oculopharyngeal muscular dystrophy.

Myopathic changes associated with psychomotor delay and seizures caused by a novel homozygous mutation in TBCK.

BACKGROUND: Biallelic mutations in TBC1-domain containing kinase (TBCK) lead to hypotonia, global developmental delay with severe cognitive and motor deficits, and variable presentation of dysmorphic facial features and brain malformations. It remains unclear whether hypotonia in these individuals is purely neurogenic, or also caused by progressive muscle disease. METHODS: Whole exome sequencing was performed on a family diagnosed with nonspecific myopathic changes by means of histological analysis and immunohistochemistry of muscle biopsy samples. RESULTS: A novel homozygous truncation in TBCK was found in two sisters diagnosed with muscle disease and severe psychomotor delay. TBCK was completely absent in these patients. CONCLUSIONS: Our findings identify a novel early truncating variant in TBCK associated with a severe presentation and add muscle disease to the variability of phenotypes associated with TBCK mutations. Inconsistent genotype/phenotype correlation could be ascribed to the multiple roles of TBCK in intracellular signaling and endolysosomal function in different tissues.

Zc3h10 is a novel mitochondrial regulator.

Mitochondria are the energy-generating hubs of the cell. In spite of considerable advances, our understanding of the factors that regulate the molecular circuits that govern mitochondrial function remains incomplete. Using a genome-wide functional screen, we identify the poorly characterized protein Zinc finger CCCH-type containing 10 (Zc3h10) as regulator of mitochondrial physiology. We show that Zc3h10 is upregulated during physiological mitochondriogenesis as it occurs during the differentiation of myoblasts into myotubes. Zc3h10 overexpression boosts mitochondrial function and promotes myoblast differentiation, while the depletion of Zc3h10 results in impaired myoblast differentiation, mitochondrial dysfunction, reduced expression of electron transport chain (ETC) subunits, and blunted TCA cycle flux. Notably, we have identified a loss-of-function mutation of Zc3h10 in humans (Tyr105 to Cys105) that is associated with increased body mass index, fat mass, fasting glucose, and triglycerides. Isolated peripheral blood mononuclear cells from individuals homozygotic for Cys105 display reduced oxygen consumption rate, diminished expression of some ETC subunits, and decreased levels of some TCA cycle metabolites, which all together derive in mitochondrial dysfunction. Taken together, our study identifies Zc3h10 as a novel mitochondrial regulator.

Connection between the Gut Microbiome, Systemic Inflammation, Gut Permeability and FOXP3 Expression in Patients with Primary Sjögren's Syndrome.

The aims of this study were to explore intestinal microbial composition and functionality in primary Sjögren's syndrome (pSS) and to relate these findings to inflammation, permeability and the transcription factor Forkhead box protein P3 (FOXP3) gene expression in peripheral blood. The study included 19 pSS patients and 19 healthy controls matched for age, sex, and body mass index. Fecal bacterial DNA was extracted and analyzed by 16S rRNA sequencing using an Ion S5 platform followed by a bioinformatics analysis using Quantitative Insights into Microbial Ecology (QIIME II) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Our data suggest that the gut microbiota of pSS patients differs at both the taxonomic and functional levels with respect to healthy controls. The gut microbiota profile of our pSS patients was characterized by a lower diversity and richness and with Bacteroidetes dominating at the phylum level. The pSS patients had less beneficial or commensal butyrate-producing bacteria and a higher proportion of opportunistic pathogens with proinflammatory activity, which may impair intestinal barrier function and therefore contribute to inflammatory processes associated with pSS by increasing the production of proinflammatory cytokines and decreasing the release of the anti-inflammatory cytokine IL-10 and the peripheral FOXP3 mRNA expression, implicated in the development and function of regulatory T cells (Treg) cells. Further studies are needed to better understand the real impact of dysbiosis on the course of pSS and to conceive preventive or therapeutic strategies to counteract microbiome-driven inflammation.

HDAC8 regulates canonical Wnt pathway to promote differentiation in skeletal muscles.

Histone deacetylase 8 (HDAC8) is a class 1 histone deacetylase and a member of the cohesin complex. HDAC8 is expressed in smooth muscles, but its expression in skeletal muscle has not been described. We have shown for the first time that HDAC8 is expressed in human and zebrafish skeletal muscles. Using RD/12 and RD/18 rhabdomyosarcoma cells with low and high differentiation potency, respectively, we highlighted a specific correlation with HDAC8 expression and an advanced stage of muscle differentiation. We inhibited HDAC8 activity through a specific PCI-34051 inhibitor in murine C2C12 myoblasts and zebrafish embryos, and we observed skeletal muscles differentiation impairment. We also found a positive regulation of the canonical Wnt signaling by HDAC8 that might explain muscle differentiation defects. These findings suggest a novel mechanism through which HDAC8 expression, in a specific time window of skeletal muscle development, positively regulates canonical Wnt pathway that is necessary for muscle differentiation.

Development and Validation of the Overall Foot Health Questionnaire for Patients with Rheumatoid Arthritis: A Cross-Sectional Descriptive Analysis.

Background and Objectives: In general, patients with rheumatoid arthritis (RA) are ignorant of the physician's role and of RA-related feet problems. The aim of our study was to validate a questionnaire on the knowledge of different aspects of overall foot health in patients with RA. Materials and Methods: A cross-sectional descriptive analysis was carried out between March 2017 and April 2017. A questionnaire was designed and validated through the Delphi method to evaluate the knowledge about the illness, the repercussions on feet, medical podiatry care, and the role of the medical podiatrist. Results: After being checked by a panel of experts, all the items obtained a Cronbach's alpha over 0.70. Conclusions: The content of this questionnaire about the knowledge of different aspects of medical podiatry health in patients with RA has internal consistency.

ORAI1 Mutations with Distinct Channel Gating Defects in Tubular Aggregate Myopathy.

Calcium (Ca2+ ) is a physiological key factor, and the precise modulation of free cytosolic Ca2+ levels regulates multiple cellular functions. Store-operated Ca2+ entry (SOCE) is a major mechanism controlling Ca2+ homeostasis, and is mediated by the concerted activity of the Ca2+ sensor STIM1 and the Ca2+ channel ORAI1. Dominant gain-of-function mutations in STIM1 or ORAI1 cause tubular aggregate myopathy (TAM) or Stormorken syndrome, whereas recessive loss-of-function mutations are associated with immunodeficiency. Here, we report the identification and functional characterization of novel ORAI1 mutations in TAM patients. We assess basal activity and SOCE of the mutant ORAI1 channels, and we demonstrate that the G98S and V107M mutations generate constitutively permeable ORAI1 channels, whereas T184M alters the channel permeability only in the presence of STIM1. These data indicate a mutation-dependent pathomechanism and a genotype/phenotype correlation, as the ORAI1 mutations associated with the most severe symptoms induce the strongest functional cellular effect. Examination of the non-muscle features of our patients strongly suggests that TAM and Stormorken syndrome are spectra of the same disease. Overall, our results emphasize the importance of SOCE in skeletal muscle physiology, and provide new insights in the pathomechanisms involving aberrant Ca2+ homeostasis and leading to muscle dysfunction.

Multidisciplinary study of a new ClC-1 mutation causing myotonia congenita: a paradigm to understand and treat ion channelopathies.

Myotonia congenita is an inherited disease that is characterized by impaired muscle relaxation after contraction caused by loss-of-function mutations in the skeletal muscle ClC-1 channel. We report a novel ClC-1 mutation, T335N, that is associated with a mild phenotype in 1 patient, located in the extracellular I-J loop. The purpose of this study was to provide a solid correlation between T335N dysfunction and clinical symptoms in the affected patient as well as to offer hints for drug development. Our multidisciplinary approach includes patch-clamp electrophysiology on T335N and ClC-1 wild-type channels expressed in tsA201 cells, Western blot and quantitative PCR analyses on muscle biopsies from patient and unaffected individuals, and molecular dynamics simulations using a homology model of the ClC-1 dimer. T335N channels display reduced chloride currents as a result of gating alterations rather than altered surface expression. Molecular dynamics simulations suggest that the I-J loop might be involved in conformational changes that occur at the dimer interface, thus affecting gating. Finally, the gene expression profile of T335N carrier showed a diverse expression of K+ channel genes, compared with control individuals, as potentially contributing to the phenotype. This experimental paradigm satisfactorily explained myotonia in the patient. Furthermore, it could be relevant to the study and therapy of any channelopathy.-Imbrici, P., Altamura, C., Camerino, G. M., Mangiatordi, G. F., Conte, E., Maggi, L., Brugnoni, R., Musaraj, K., Caloiero, R., Alberga, D., Marsano, R. M., Ricci, G., Siciliano, G., Nicolotti, O., Mora, M., Bernasconi, P., Desaphy, J.-F., Mantegazza, R., Camerino, D. C. Multidisciplinary study of a new ClC-1 mutation causing myotonia congenita: a paradigm to understand and treat ion channelopathies.

The italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis.

INTRODUCTION: Limb girdle muscular dystrophies (LGMDs) are characterized by high molecular heterogeneity, clinical overlap, and a paucity of specific biomarkers. Their molecular definition is fundamental for prognostic and therapeutic purposes. METHODS: We created an Italian LGMD registry that included 370 molecularly defined patients. We reviewed detailed retrospective and prospective data and compared each LGMD subtype for differential diagnosis purposes. RESULTS: LGMD types 2A and 2B are the most frequent forms in Italy. The ages at disease onset, clinical progression, and cardiac and respiratory involvement can vary greatly between each LGMD subtype. In a set of extensively studied patients, targeted next-generation sequencing (NGS) identified mutations in 36.5% of cases. CONCLUSION: Detailed clinical characterization combined with muscle tissue analysis is fundamental to guide differential diagnosis and to address molecular tests. NGS is useful for diagnosing forms without specific biomarkers, although, at least in our study cohort, several LGMD disease mechanisms remain to be identified. Muscle Nerve 55: 55-68, 2017.

Rare Disease Biospecimens and Patient Registries: Interoperability for Research Promotion, a European Example: EuroBioBank and SpainRDR-BioNER.

Well-annotated and properly preserved specimens are crucial both for diagnostic purposes and for use in basic and pre-clinical research, and are especially important for rare disease (RD) studies. Several consortia have been established in the recent years in order to facilitate research and to maximise access to rare biological samples and data stored in rare disease biobanks and registries, among them the EuroBioBank network and the Spain National Rare Disease Registry (RDR) and Biobank (BioNER).EuroBioBank, established in 2001, was the first network of RD biobanks to operate in Europe as a service distributing human DNA, cells, and tissue to the scientific community conducting research on rare diseases.The Spanish RDR and BioNER were created for facilitating rare disease research and health-related matters. The coordination of these two bodies represents an example of great scientific value as biological samples donated by patients at BioNER are linked to clinical information collected in the RDR.Rare disease biobanks and registries will need for the future to increase their effort to improve interconnection so to enable investigators to better locate samples and associated data, while protecting security of the data and privacy of the participants and adhering to international ethical and legal requirements.