The following publications are the result of the successful cooperation of the Solve-RD partners and represent the breadth of the scientific expertise of the consortium.
Loss of function variants in DNAJB4 cause a myopathy with early respiratory failure
The European Genome-phenome Archive in 2021
A Recurrent KPNA3 Missense Variant Causing Infantile Pure Spastic Paraplegia
doi: 10.1002/ana.26297. Epub 2022 Jan 20.
Novel insights into PORCN mutations, associated phenotypes and pathophysiological aspects
Recessive variants in COL25A1 gene as novel cause of arthrogryposis multiplex congenita with ocular congenital cranial dysinnervation disorder
doi: 10.1002/humu.24333. Epub 2022 Feb 3.
Genetic diagnosis in Sudanese and Tunisian families with syndromic intellectual disability through exome sequencing
doi: 10.1111/ahg.12460. Epub 2022 Feb 3.
Clinical practice guideline for the management of paediatric Charcot-Marie-Tooth disease
doi: 10.1136/jnnp-2021-328483. Epub 2022 Feb 9.
NCAM1 and GDF15 are biomarkers of Charcot-Marie-Tooth disease in patients and mice
doi: 10.1093/brain/awac055. Online ahead of print.
De Novo and Dominantly Inherited SPTAN1 Mutations Cause Spastic Paraplegia and Cerebellar Ataxia
doi: 10.1002/mds.28959. Epub 2022 Feb 12.
Characteristics of serum neurofilament light chain as a biomarker in hereditary spastic paraplegia type 4
doi: 10.1002/acn3.51518. Epub 2022 Feb 16.
Medical costs of children admitted to the neonatal intensive care unit: The role and possible economic impact of WES in early diagnosis
doi: 10.1016/j.ejmg.2022.104467. Epub 2022 Mar 1.
Solving the genetic aetiology of hereditary gastrointestinal tumour syndromes- a collaborative multicentre endeavour within the project Solve-RD
doi: 10.1016/j.ejmg.2022.104475. Epub 2022 Mar 11.
RFC1 repeat expansions: A recurrent cause of sensory and autonomic neuropathy with cough and ataxia
doi: 10.1111/ene.15310. Epub 2022 Mar 23.
Paving the Way Toward Meaningful Trials in Ataxias: An Ataxia Global Initiative Perspective
doi: 10.1002/mds.29032. Epub 2022 Apr 27.
SvAnna: efficient and accurate pathogenicity prediction of coding and regulatory structural variants in long-read genome sequencing
Clinical and genetic spectra of 1550 index patients with hereditary spastic paraplegia
Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases
How to proceed after "negative" exome: A review on genetic diagnostics, limitations, challenges, and emerging new multiomics techniques
doi: 10.1002/jimd.12507. Epub 2022 May 22.
Co-designing models for the communication of genomic results for rare diseases: a comparative study in the Czech Republic and the United Kingdom
doi: 10.1007/s12687-022-00589-w. Epub 2022 May 6.
Recommendations for whole genome sequencing in diagnostics for rare diseases
doi: 10.1038/s41431-022-01113-x. Epub 2022 May 16.
High diagnostic rate of trio exome sequencing in consanguineous families with neurogenetic diseases
The RD-Connect Genome-Phenome Analysis Platform: Accelerating diagnosis, research, and gene discovery for rare diseases
The GA4GH Phenopacket schema defines a computable representation of clinical data
The Human Phenotype Ontology in 2021
RNA-seq in DMD urinary stem cells recognized muscle-related transcription signatures and addressed the identification of atypical mutations by whole-genome sequencing
doi: 10.1016/j.xhgg.2021.100054. eCollection 2022 Jan 13.
Human disease genes website series: An international, open and dynamic library for up-to-date clinical information
doi: 10.1002/ajmg.a.62057. Epub 2021 Jan 13.
Linked-Read Whole Genome Sequencing Solves a Double DMD Gene Rearrangement
Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease
Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction
doi: 10.1016/j.ajhg.2021.01.007. Epub 2021 Jan 28.
Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries
doi: 10.1212/NXG.0000000000000536. eCollection 2021 Feb.
Quantitative facial phenotyping for Koolen-de Vries and 22q11.2 deletion syndrome
doi: 10.1038/s41431-021-00824-x. Epub 2021 Feb 18.
TAOK1 is associated with neurodevelopmental disorder and essential for neuronal maturation and cortical development
doi: 10.1002/humu.24176. Epub 2021 Mar 1.
A weakened interface in the P182L variant of HSP27 associated with severe Charcot-Marie-Tooth neuropathy causes aberrant binding to interacting proteins
doi: 10.15252/embj.2019103811. Epub 2021 Mar 1.
Spinocerebellar ataxia type 14: refining clinicogenetic diagnosis in a rare adult-onset disorder
doi: 10.1002/acn3.51315. Epub 2021 Mar 19.
A de novo STUB1 variant associated with an early adult-onset multisystemic ataxia phenotype
Systematic analysis of short tandem repeats in 38,095 exomes provides an additional diagnostic yield
doi: 10.1038/s41436-021-01174-1. Epub 2021 Apr 12.
Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature
doi: 10.1016/j.ajhg.2021.04.008. Epub 2021 Apr 27.
Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges
doi: 10.1002/1878-0261.12948. Epub 2021 May 2.
Modeling seizures in the Human Phenotype Ontology according to contemporary ILAE concepts makes big phenotypic data tractable
doi: 10.1111/epi.16908. Epub 2021 May 5.
Nephroplex: a kidney-focused NGS panel highlights the challenges of PKD1 sequencing and identifies a founder BBS4 mutation
doi: 10.1007/s40620-021-01048-4. Epub 2021 May 8.
Solving unsolved rare neurological diseases-a Solve-RD viewpoint
doi: 10.1038/s41431-021-00901-1. Epub 2021 May 10.
Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia.
Missense mutations in small muscle protein X-linked (SMPX) cause distal myopathy with protein inclusions
doi: 10.1007/s00401-021-02319-x. Epub 2021 May 11.
High prevalence of sporadic late-onset nemaline myopathy in a cohort of whole-exome sequencing negative myopathy patients
doi: 10.1016/j.nmd.2021.04.010. Epub 2021 May 14.
Unrestrained poly-ADP-ribosylation provides insights into chromatin regulation and human disease
doi: 10.1016/j.molcel.2021.04.028. Epub 2021 May 20.
Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder
doi: 10.1016/j.ajhg.2021.04.024. Epub 2021 May 21.
Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1)
doi: 10.1038/s41431-021-00851-8. Epub 2021 Jun 1.
A mosaic PIK3CA variant in a young adult with diffuse gastric cancer: case report
doi: 10.1038/s41431-021-00853-6. Epub 2021 Jun 1.
A MT-TL1 variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesis
doi: 10.1038/s41431-021-00900-2. Epub 2021 Jun 1.
Solving patients with rare diseases through programmatic reanalysis of genome-phenome data
doi: 10.1038/s41431-021-00852-7. Epub 2021 Jun 1.
Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases
doi: 10.1038/s41431-021-00859-0. Epub 2021 Jun 1.
Recurrent KCNT2 missense variants affecting p.Arg190 result in a recognizable phenotype
doi: 10.1002/ajmg.a.62370. Epub 2021 Jun 1.
An identical-by-descent novel splice-donor variant in PRUNE1 causes a neurodevelopmental syndrome with prominent dystonia in two consanguineous Sudanese families
doi: 10.1111/ahg.12437. Epub 2021 Jun 10.
Induced pluripotent stem cell-derived motor neurons of CMT type 2 patients reveal progressive mitochondrial dysfunction
Biallelic loss-of-function variations in PRDX3 cause cerebellar ataxia
The ARCA Registry: A Collaborative Global Platform for Advancing Trial Readiness in Autosomal Recessive Cerebellar Ataxias
doi: 10.3389/fneur.2021.677551. eCollection 2021.
Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies
doi: 10.3389/fneur.2021.677551. eCollection 2021.
Genetic convergence of developmental and epileptic encephalopathies and intellectual disability
doi: 10.1111/dmcn.14989. Epub 2021 Jul 11.
Characterization of HNRNPA1 mutations defines diversity in pathogenic mechanisms and clinical presentation
Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome
Congenital anomalies and genetic disorders in neonates and infants: a single-center observational cohort study
doi: 10.1007/s00431-021-04213-w. Epub 2021 Aug 4.
Biallelic ADPRHL2 mutations in complex neuropathy affect ADP ribosylation and DNA damage response
doi: 10.26508/lsa.202101057. Print 2021 Nov.
The CDH1 c.1901C>T Variant: A Founder Variant in the Portuguese Population with Severe Impact in mRNA Splicing
Detection of mobile elements insertions for routine clinical diagnostics in targeted sequencing data
doi: 10.1002/mgg3.1807. Epub 2021 Sep 7.
A de novo CSDE1 variant causing neurodevelopmental delay, intellectual disability, neurologic and psychiatric symptoms in a child of consanguineous parents
doi: 10.1002/ajmg.a.62494. Epub 2021 Sep 14.
Establishing the phenotypic spectrum of ZTTK syndrome by analysis of 52 individuals with variants in SON
doi: 10.1038/s41431-021-00960-4. Epub 2021 Sep 15.
Preparing n-of-1 Antisense Oligonucleotide Treatments for Rare Neurological Diseases in Europe: Genetic, Regulatory, and Ethical Perspectives
doi: 10.1089/nat.2021.0039. Epub 2021 Sep 29.
Out-of-Frame Mutations in ACTN2 Last Exon Cause a Dominant Distal Myopathy With Facial Weakness
doi: 10.1212/NXG.0000000000000619. eCollection 2021 Oct.
Biallelic TMEM260 variants cause truncus arteriosus, with or without renal defects
doi: 10.1111/cge.14071. Epub 2021 Oct 11.
Assessment of Sacsin Turnover in Patients With ARSACS: Implications for Molecular Diagnosis and Pathogenesis
doi: 10.1212/WNL.0000000000012962. Epub 2021 Oct 14.
Lessons learned from unsolicited findings in clinical exome sequencing of 16,482 individuals
doi: 10.1038/s41431-021-00964-0. Epub 2021 Oct 25.
Economic evaluations of exome and genome sequencing in pediatric genetics: considerations towards a consensus strategy
Interpretable prioritization of splice variants in diagnostic next-generation sequencing
RNF170-Related Hereditary Spastic Paraplegia: Confirmation by a Novel Mutation
Homozygous WASHC4 variant in two sisters causes a syndromic phenotype defined by dysmorphisms, intellectual disability, profound developmental disorder, and skeletal muscle involvement
Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH: A Longitudinal Multicentre Study
Phenotype based prediction of exome sequencing outcome using machine learning for neurodevelopmental disorders
Long-read trio sequencing of individuals with unsolved intellectual disability.
doi: 10.1038/s41431-020-00770-0. Epub 2020 Nov 30.
Elucidating the clinical spectrum and molecular basis of HYAL2 deficiency.
doi: 10.1016/j.gim.2021.10.014. Epub 2021 Nov 30.
Genome-wide variant calling in reanalysis of exome sequencing data uncovered a pathogenic TUBB3 variant
doi: 10.1016/j.ejmg.2021.104402. Epub 2021 Dec 1.
Gastric cancer genetic predisposition and clinical presentations: Established heritable causes and potential candidate genes
doi: 10.1016/j.ejmg.2021.104401. Epub 2021 Dec 3.
Confirmation of TACO1 as a Leigh Syndrome Disease Gene in Two Additional Families.
Delineating MT-ATP6-associated disease: From isolated neuropathy to early onset neurodegeneration.
doi: 10.1212/NXG.0000000000000393. eCollection 2020 Feb.
Aicardi-Goutières syndrome due to a paternal mosaic IFIH1 mutation.
doi: 10.1212/NXG.0000000000000384. eCollection 2020 Feb.
Towards a European health research and innovation cloud.
Genome Med. 2020 Feb 19;12(1):18. doi: 10.1186/s13073-020-0713-z.
Lipids in the Physiopathology of Hereditary Spastic Paraplegias
Impairment of Lysosome Function and Autophagy in Rare Neurodegenerative Diseases.
A pipeline‐friendly software tool for genome diagnostics to prioritize genes by matching patient symptoms to literature.
K. Joeri van der Velde, Sander van den Hoek, Freerk van Dijk, Dennis Hendriksen, Cleo C. van Diemen, Lennart F. Johansson, Kristin M. Abbott, Patrick Deelen, Birgit Sikkema-Raddatz, Morris A. Swertz
ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy.
Small heat shock proteins in neurodegenerative diseases.
doi: 10.1007/s12192-020-01101-4. Epub 2020 Apr 22.
Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes.
Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging
Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging.
BAG3 Pro209 mutants associated with myopathy and neuropathy relocate chaperones of the CASA-complex to aggresomes.
Sci Rep. 2020 May 29;10(1):8755. doi: 10.1038/s41598-020-65664-z.
Urine concentrating defect as presenting sign of progressive renal failure in Bardet-Biedl syndrome patients
doi: 10.1093/ckj/sfaa182. eCollection 2021 Jun.
A Genetics-First Approach Revealed Monogenic Disorders in Patients With ARM and VACTERL Anomalies.
doi: 10.3389/fped.2020.00310. eCollection 2020.
Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage in humans and mice.
Clinico-Genetic, Imaging and Molecular Delineation of COQ8A-Ataxia: A Multicenter Study of 59 Patients.
doi: 10.1002/ana.25751. Epub 2020 Jun 10.
De Novo Variants in CNOT1, a Central Component of the CCR4-NOT Complex Involved in Gene Expression and RNA and Protein Stability, Cause Neurodevelopmental Delay.
doi: 10.1016/j.ajhg.2020.05.017. Epub 2020 Jun 17.
Whole-genome sequencing of patients with rare diseases in a national health system.
doi: 10.1038/s41586-020-2434-2. Epub 2020 Jun 24.
Improved Diagnosis of Rare Disease Patients through Systematic Detection of Runs of Homozygosity.
Tumor Necrosis Factor Receptor SF10A (TNFRSF10A) SNPs Correlate With Corticosteroid Response in Duchenne Muscular Dystrophy.
doi: 10.3389/fgene.2020.00605. eCollection 2020.
Behr syndrome and hypertrophic cardiomyopathy in a family with a novel UCHL1 deletion.
doi: 10.1007/s00415-020-10059-3. Epub 2020 Jul 12.
ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population
doi: 10.1038/s41431-020-0691-z. Epub 2020 Jul 17.
A guide to writing systematic reviews of rare disease treatments to generate FAIR-compliant datasets: building a Treatabolome.
Orphanet J Rare Dis. 2020 Aug 12;15(1):206. doi:10.1186/s13023-020-01493-7.
Presence of Genetic Variants Among Young Men With Severe COVID-19.
Analysis of brain atrophy and local gene expression in genetic frontotemporal dementia.
Brain Commun. 2020 Aug 19;2(2):fcaa122. doi:10.1093/braincomms/fcaa122
The position of nonsense mutations can predict the phenotype severity: A survey on the DMD gene.
doi: 10.1371/journal.pone.0237803. eCollection 2020.
Evidence for 28 genetic disorders discovered by combining healthcare and research data.
doi: 10.1038/s41586-020-2832-5. Epub 2020 Oct 14.
Novel Homozygous Missense Mutation in the ARG1 Gene in a Large Sudanese Family.
Generation of the CRISPR/Cas9-mediated KIF1C knock-out human iPSC line HIHRSi003-A-1.
doi: 10.1016/j.scr.2020.102059. Epub 2020 Oct 29.
Candidate Gene Discovery in Hereditary Colorectal Cancer and Polyposis Syndromes-Considerations for Future Studies.
The 2021 version of the gene table of neuromuscular disorders (nuclear genome).
Neuromuscul Disord. 2020 Dec;30(12):1008-1048. doi: 10.1016/j.nmd.2020.11.009.
Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores
Am J Hum Genet. 2020 Dec 3;107(6):1078-1095.
doi: 10.1016/j.ajhg.2020.11.002. Epub 2020 Nov 19.
PCYT2 mutations disrupting etherlipid biosynthesis: phenotypes converging on the CDP-ethanolamine pathway
Brain. 2021 Mar 3;144(2):e17.
Defects in Axonal Transport in Inherited Neuropathies.
J Neuromuscul Dis. 2019;6(4):401-419. doi: 10.3233/JND-190427.
Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.
Recommendations for patient screening in ultra-rare inherited metabolic diseases: what have we learned from Niemann-Pick disease type C?
Targeted therapies for congenital myasthenic syndromes: systematic review and steps towards a treatabolome.
doi: 10.1042/ETLS20180100. Epub 2019 Jan 28.
Neuropathy-causing mutations in HSPB1 impair autophagy by disturbing the formation of SQSTM1/p62 bodies.
Biallelic VARS variants cause developmental encephalopathy with microcephaly that is recapitulated in vars knockout zebrafish.
Sensory neuropathy-causing mutations in ATL3 affect ER-mitochondria contact sites and impair axonal mitochondrial distribution.
Autosomal Recessive Cerebellar Ataxias: Paving the Way toward Targeted Molecular Therapies.
Update on the Genetics of Spastic Paraplegias.
Truncating Mutations in UBAP1 Cause Hereditary Spastic Paraplegia.
Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8 + T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness
doi: 10.1016/j.immuni.2019.03.005. Epub 2019 Apr 2.
Novel likely pathogenic variants in TMEM126A identified in non-syndromic autosomal recessive optic atrophy: two case reports.
Hereditary spastic paraplegias: time for an objective case definition and a new nosology for neurogenetic disorders to facilitate biomarker/therapeutic studies.
Expert Rev Neurother. 2019 May;19(5):409-415. doi: 10.1080/14737175.2019.1608824. Epub 2019 Apr 30.
Long-Read Sequencing Emerging in Medical Genetics.
Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7
Somatic mutational signatures in polyposis and colorectal cancer.
Congenital myopathy with hanging big toe due to homozygous myopalladin (MYPN) mutation.
FAHN/SPG35: a narrow phenotypic spectrum across disease classifications.
Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies.
Genome Med. 2019 Jun 17;11(1):38. doi: 10.1186/s13073-019-0649-3.
Increasing phenotypic annotation improves the diagnostic rate of exome sequencing in a rare neuromuscular disorder.
doi: 10.1002/humu.23792. Epub 2019 Jun 23.
RegulationSpotter: annotation and interpretation of extratranscriptic DNA variants.
Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia
Generation of two iPSC lines derived from two unrelated patients with Gaucher disease.
doi: 10.1016/j.scr.2018.10.021. Epub 2018 Nov 18.
Spastic paraplegia due to recessive or dominant mutations in ERLIN2 can convert to ALS.
Neurol Genet. 2019 Nov 13;5(6):e374. doi: 10.1212/NXG.0000000000000374.
Phenotero: Annotate as you write.
doi: 10.1111/cge.13471. Epub 2018 Dec 7.
The 2020 version of the gene table of neuromuscular disorders (nuclear genome).
Improved ontology-based similarity calculations using a study-wise annotation model.
Challenges in modelling the Charcot-Marie-Tooth neuropathies for therapy development.
doi: 10.1136/jnnp-2018-318834. Epub 2018 Jul 17.
De novo ITPR1 variants are a recurrent cause of early-onset ataxia, acting via loss of channel function.
doi: 10.1038/s41431-018-0206-3. Epub 2018 Jun 20.
Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome.
Am J Hum Genet. 2018 Sep 6;103(3):431-439. doi: 10.1016/j.ajhg.2018.07.010. Epub 2018 Aug 9.
Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report.
A nomenclature and classification for the congenital myasthenic syndromes: preparing for FAIR data in the genomic era.