De novo complex intra chromosomal rearrangement after ICSI: characterisation by BACs micro array-CGH

<p>Abstract</p> <p>Background</p> <p>In routine Assisted Reproductive Technology (ART) men with severe oligozoospermia or azoospermia should be informed about the risk of de novo congenital or chromosomal abnormalities in ICSI program. Also the benefits of preimplantation or prenatal genetic diagnosis practice need to be explained to the couple.</p> <p>Methods</p> <p>From a routine ICSI attempt, using ejaculated sperm from male with severe oligozoospermia and having normal karyotype, a 30 years old pregnant woman was referred to prenatal diagnosis in the 17^thweek for bichorionic biamniotic twin gestation. Amniocentesis was performed because of the detection of an increased foetal nuchal translucency for one of the fetus by the sonographic examination during the 12^thweek of gestation (WG). Chromosome and DNA studies of the fetus were realized on cultured amniocytes</p> <p>Results</p> <p>Conventional, molecular cytogenetic and microarray CGH experiments allowed us to conclude that the fetus had a <it>de novo </it>pericentromeric inversion associated with a duplication of the 9p22.1-p24 chromosomal region, 46,XY,invdup(9)(p22.1p24) [arrCGH 9p22.1p24 (RP11-130C19 → RP11-87O1)x3]. As containing the critical 9p22 region, our case is in coincidence with the general phenotype features of the partial trisomy 9p syndrome with major growth retardation, microcephaly and microretrognathia.</p> <p>Conclusion</p> <p>This de novo complex chromosome rearrangement illustrates the possible risk of chromosome or gene defects in ICSI program and the contribution of array-CGH for mapping rapidly de novo chromosomal imbalance.</p

Retinoblastoma

Retinoblastoma is a rare eye tumor of childhood that arises in the retina. It is the most common intraocular malignancy of infancy and childhood; with an incidence of 1/15,000–20,000 live births. The two most frequent symptoms revealing retinoblastoma are leukocoria and strabismus. Iris rubeosis, hypopyon, hyphema, buphthalmia, orbital cellulites and exophthalmia may also be observed. Sixty per cent of retinoblastomas are unilateral and most of these forms are not hereditary (median age at diagnosis two years). Retinoblastoma is bilateral in 40% of cases (median age at diagnosis one year). All bilateral and multifocal unilateral forms are hereditary. Hereditary retinoblastoma constitutes a cancer predisposition syndrome: a subject constitutionally carrying an RB1 gene mutation has a greater than 90% risk of developing retinoblastoma but is also at increased risk of developing other types of cancers. Diagnosis is made by fundoscopy. Ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) scans may contribute to diagnosis. Management of patients with retinoblastoma must take into account the various aspects of the disease: the visual risk, the possibly hereditary nature of the disease, the life-threatening risk. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is taken according to the histological risk factors. Conservative treatment for at least one eye is possible in most of the bilateral cases. It includes laser alone or combined with chemotherapy, cryotherapy and brachytherapy. The indication for external beam radiotherapy should be restricted to large ocular tumors and diffuse vitreous seeding because of the risk of late effects, including secondary sarcoma. Vital prognosis, related to retinoblastoma alone, is now excellent in patients with unilateral or bilateral forms of retinoblastoma. Long term follow-up and early counseling regarding the risk of second primary tumors and transmission should be offered to retinoblastoma patients

The future of botanical monography : report from an international workshop, 12–16 March 2012, Smolenice, Slovak Republic

Monographs are fundamental for progress in systematic botany. They are the vehicles for circumscribing and naming taxa, determining distributions and ecology, assessing relationships for formal classification, and interpreting long-term and short-term dimensions of the evolutionary process. Despite their importance, fewer monographs are now being prepared by the newer generation of systematic botanists, who are understandably involved principally with DNA data and analysis, especially for answering phylogenetic, biogeographic, and population genetic questions. As monographs provide hypotheses regarding species boundaries and plant relationships, new insights in many plant groups are urgently needed. Increasing pressures on biodiversity, especially in tropical and developing regions of the world, emphasize this point. The results from a workshop (with 21 participants) reaffirm the central role that monographs play in systematic botany. But, rather than advocating abbreviated models for monographic products, we recommend a full presentation of relevant information. Electronic publication offers numerous means of illustration of taxa, habitats, characters, and statistical and phylogenetic analyses, which previously would have been prohibitively costly. Open Access and semantically enhanced linked electronic publications provide instant access to content from anywhere in the world, and at the same time link this content to all underlying data and digital resources used in the work. Resources in support of monography, especially databases and widely and easily accessible digital literature and specimens, are now more powerful than ever before, but interfacing and interoperability of databases are much needed. Priorities for new resources to be developed include an index of type collections and an online global chromosome database. Funding for sabbaticals for monographers to work uninterrupted on major projects is strongly encouraged. We recommend that doctoral students be assigned smaller genera, or natural portions of larger ones (subgenera, sections, etc.), to gain the necessary expertise for producing a monograph, including training in a broad array of data collection (e.g., morphology, anatomy, palynology, cytogenetics, DNA techniques, ecology, biogeography), data analysis (e.g., statistics, phylogenetics, models), and nomenclature. Training programs, supported by institutes, associations, and agencies, provide means for passing on procedures and perspectives of challenging botanical monography to the next generation of young systematists.Appreciation is expressed to: the Andrew W. Mellon Foundation for financial support that allowed the workshop to be convened; the International Association for Plant Taxonomy (IAPT) for additional financial support for the workshop.http://www.botanik.univie.ac.at/iapt/s_taxon.phpam201

The future of botanical monography : report from an international workshop, 12–16 March 2012, Smolenice, Slovak Republic

Monographs are fundamental for progress in systematic botany. They are the vehicles for circumscribing and naming taxa, determining distributions and ecology, assessing relationships for formal classification, and interpreting long-term and short-term dimensions of the evolutionary process. Despite their importance, fewer monographs are now being prepared by the newer generation of systematic botanists, who are understandably involved principally with DNA data and analysis, especially for answering phylogenetic, biogeographic, and population genetic questions. As monographs provide hypotheses regarding species boundaries and plant relationships, new insights in many plant groups are urgently needed. Increasing pressures on biodiversity, especially in tropical and developing regions of the world, emphasize this point. The results from a workshop (with 21 participants) reaffirm the central role that monographs play in systematic botany. But, rather than advocating abbreviated models for monographic products, we recommend a full presentation of relevant information. Electronic publication offers numerous means of illustration of taxa, habitats, characters, and statistical and phylogenetic analyses, which previously would have been prohibitively costly. Open Access and semantically enhanced linked electronic publications provide instant access to content from anywhere in the world, and at the same time link this content to all underlying data and digital resources used in the work. Resources in support of monography, especially databases and widely and easily accessible digital literature and specimens, are now more powerful than ever before, but interfacing and interoperability of databases are much needed. Priorities for new resources to be developed include an index of type collections and an online global chromosome database. Funding for sabbaticals for monographers to work uninterrupted on major projects is strongly encouraged. We recommend that doctoral students be assigned smaller genera, or natural portions of larger ones (subgenera, sections, etc.), to gain the necessary expertise for producing a monograph, including training in a broad array of data collection (e.g., morphology, anatomy, palynology, cytogenetics, DNA techniques, ecology, biogeography), data analysis (e.g., statistics, phylogenetics, models), and nomenclature. Training programs, supported by institutes, associations, and agencies, provide means for passing on procedures and perspectives of challenging botanical monography to the next generation of young systematists.Appreciation is expressed to: the Andrew W. Mellon Foundation for financial support that allowed the workshop to be convened; the International Association for Plant Taxonomy (IAPT) for additional financial support for the workshop.http://www.botanik.univie.ac.at/iapt/s_taxon.phpam201

Solving patients with rare diseases through programmatic reanalysis of genome-phenome data.

Funder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health); doi: https://doi.org/10.13039/100011272; Grant(s): 305444, 305444Funder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329Funder: Generalitat de Catalunya (Government of Catalonia); doi: https://doi.org/10.13039/501100002809Funder: EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj); doi: https://doi.org/10.13039/501100008530Funder: Instituto Nacional de Bioinformática ELIXIR Implementation Studies Centro de Excelencia Severo OchoaFunder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health)Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics

Solving unsolved rare neurological diseases-a Solve-RD viewpoint.

Funder: Durch Princess Beatrix Muscle Fund Durch Speeren voor Spieren Muscle FundFunder: University of Tübingen Medical Faculty PATE programFunder: European Reference Network for Rare Neurological Diseases | 739510Funder: European Joint Program on Rare Diseases (EJP-RD COFUND-EJP) | 44140962

Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases.

For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient's data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together >300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four European Reference Networks (ERNs; ERN-ITHACA, ERN-RND, ERN-Euro NMD, ERN-GENTURIS) which annually see more than 270,000 RD patients with respective pathologies. The main ambition is to solve unsolved rare diseases for which a molecular cause is not yet known. This is achieved through an innovative clinical research environment that introduces novel ways to organise expertise and data. Two major approaches are being pursued (i) massive data re-analysis of >19,000 unsolved rare disease patients and (ii) novel combined -omics approaches. The minimum requirement to be eligible for the analysis activities is an inconclusive exome that can be shared with controlled access. The first preliminary data re-analysis has already diagnosed 255 cases form 8393 exomes/genome datasets. This unprecedented degree of collaboration focused on sharing of data and expertise shall identify many new disease genes and enable diagnosis of many so far undiagnosed patients from all over Europe