In 2016, guidelines for diagnostic Next Generation Sequencing (NGS) have been published by EuroGentest in order to assist laboratories in the implementation and accreditation of NGS in a diagnostic setting. These guidelines mainly focused on Whole Exome Sequencing (WES) and targeted (gene panels) sequencing detecting small germline variants (Single Nucleotide Variants (SNVs) and insertions/deletions (indels)). Since then, Whole Genome Sequencing (WGS) has been increasingly introduced in the diagnosis of rare diseases as WGS allows the simultaneous detection of SNVs, Structural Variants (SVs) and other types of variants such as repeat expansions. The use of WGS in diagnostics warrants the re-evaluation and update of previously published guidelines. This work was jointly initiated by EuroGentest and the Horizon2020 project Solve-RD. Statements from the 2016 guidelines have been reviewed in the context of WGS and updated where necessary. The aim of these recommendations is primarily to list the points to consider for clinical (laboratory) geneticists, bioinformaticians, and (non-)geneticists, to provide technical advice, aid clinical decision-making and the reporting of the results.

• MeSH
• Exome * MeSH
• Genome, Human * MeSH
• Polymorphism, Single Nucleotide MeSH
• Humans MeSH
• Whole Genome Sequencing MeSH
• High-Throughput Nucleotide Sequencing methods   MeSH
• Rare Diseases diagnosis   genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Molecular profiling of tumor samples has acquired importance in cancer research, but currently also plays an important role in the clinical management of cancer patients. Rapid identification of genomic aberrations improves diagnosis, prognosis and effective therapy selection. This can be attributed mainly to the development of next-generation sequencing (NGS) methods, especially targeted DNA panels. Such panels enable a relatively inexpensive and rapid analysis of various aberrations with clinical impact specific to particular diagnoses. In this review, we discuss the experimental approaches and bioinformatic strategies available for the development of an NGS panel for a reliable analysis of selected biomarkers. Compliance with defined analytical steps is crucial to ensure accurate and reproducible results. In addition, a careful validation procedure has to be performed before the application of NGS targeted assays in routine clinical practice. With more focus on bioinformatics, we emphasize the need for thorough pipeline validation and management in relation to the particular experimental setting as an integral part of the NGS method establishment. A robust and reproducible bioinformatic analysis running on powerful machines is essential for proper detection of genomic variants in clinical settings since distinguishing between experimental noise and real biological variants is fundamental. This review summarizes state-of-the-art bioinformatic solutions for careful detection of the SNV/Indels and CNVs for targeted sequencing resulting in translation of sequencing data into clinically relevant information. Finally, we share our experience with the development of a custom targeted NGS panel for an integrated analysis of biomarkers in lymphoproliferative disorders.

• Keywords
• Bioinformatic analysis, CNV, Clinical application, Molecular markers, NGS, SNV/indel, Targeted panels,
• Publication type
• Journal Article MeSH

Cytogenomic investigations of haematological neoplasms, including chromosome banding analysis, fluorescence in situ hybridisation (FISH) and microarray analyses have become increasingly important in the clinical management of patients with haematological neoplasms. The widespread implementation of these techniques in genetic diagnostics has highlighted the need for guidance on the essential criteria to follow when providing cytogenomic testing, regardless of choice of methodology. These recommendations provide an updated, practical and easily available document that will assist laboratories in the choice of testing and methodology enabling them to operate within acceptable standards and maintain a quality service.

• MeSH
• Leukemia, Myeloid, Acute genetics   MeSH
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive MeSH
• Hematologic Neoplasms genetics   MeSH
• In Situ Hybridization, Fluorescence MeSH
• Humans MeSH
• Lymphoma genetics   MeSH
• Microarray Analysis MeSH
• Multiple Myeloma genetics   MeSH
• Myelodysplastic Syndromes MeSH
• Chromosome Banding MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.

• Keywords
• Assisted reproductive technology, Epigenetics, Expanded carrier screening, Female infertility, Gamete donor anonymity, Germline genome editing, Male infertility, Mitochondrial replacement therapy, Non-invasive prenatal testing, Preimplantation genetic testing,
• MeSH
• Reproductive Techniques, Assisted * MeSH
• Genetic Testing methods   MeSH
• Congresses as Topic MeSH
• Genetics, Medical methods   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively-parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.

• Keywords
• assisted reproductive technology, epigenetics, expanded carrier screening, female infertility, gamete donor anonymity, germline genome editing, male infertility, mitochondrial replacement therapy, non-invasive prenatal testing, preimplantation genetic testing,
• Publication type
• Journal Article MeSH

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.

• MeSH
• Cilia pathology   ultrastructure   MeSH
• Delphi Technique MeSH
• Diagnosis, Differential MeSH
• Fluorescent Antibody Technique MeSH
• Genetic Testing MeSH
• Kartagener Syndrome diagnosis   genetics   MeSH
• Humans MeSH
• Nitric Oxide analysis   MeSH
• Review Literature as Topic MeSH
• Societies, Medical MeSH
• Microscopy, Electron, Transmission MeSH
• Microscopy, Video MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Practice Guideline MeSH
• Geographicals
• Europe MeSH
• Names of Substances
• Nitric Oxide MeSH

• MeSH
• Genetic Testing standards   MeSH
• Humans MeSH
• Disclosure standards   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Letter MeSH
• Comment MeSH

• MeSH
• Accreditation legislation & jurisprudence   MeSH
• Biomarkers metabolism   MeSH
• Tissue Array Analysis standards   MeSH
• Cytogenetic Analysis methods   standards   MeSH
• Gene Expression MeSH
• Tissue Fixation methods   standards   MeSH
• In Situ Hybridization, Fluorescence standards   MeSH
• Humans MeSH
• Neoplasm Proteins genetics   MeSH
• Neoplasms diagnosis   genetics   pathology   MeSH
• Sensitivity and Specificity MeSH
• Biopsy, Fine-Needle standards   MeSH
• High-Throughput Nucleotide Sequencing standards   MeSH
• Research Design standards   MeSH
• Paraffin Embedding methods   standards   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Guideline MeSH
• Geographicals
• Europe MeSH
• Names of Substances
• Biomarkers MeSH
• Neoplasm Proteins MeSH