Publications
132 results found
Morris-Rosendahl DJ, Crocq M-A, 2020, Neurodevelopmental disorders-the history and future of a diagnostic concept, DIALOGUES IN CLINICAL NEUROSCIENCE, Vol: 22, Pages: 65-72, ISSN: 1294-8322
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- Citations: 105
Yazdani MF, Morris-Rosendahl D, Chen L, et al., 2020, Images of the month 1: Cough before the storm: A case of pulmonary alveolar microlithiasis, Clinical Medicine, Vol: 20, Pages: 110-111, ISSN: 1470-2118
Rubbo B, Shoemark A, Legendre M, et al., 2020, Topological Data Analysis Coupled with Machine Learning Reveals New Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Shovlin CL, Morris-Rosendahl DJ, Copeland F, et al., 2019, DELIVERING THE 100,000 GENOMES PROJECT TO ESTABLISH THE FUNCTIONAL ROLE OF DNA SEQUENCE VARIANTS IN RESPIRATORY RARE DISEASES, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A44-A45, ISSN: 0040-6376
Wallmeier J, Frank D, Shoemark A, et al., 2019, De novo mutations in FOXJ1 result in a motile ciliopathy with hydrocephalus and randomization of left/right body asymmetry, American Journal of Human Genetics, Vol: 105, Pages: 1030-1039, ISSN: 0002-9297
Nastase A, Mandal A, Lu SK, et al., 2019, Low Number of Mutations and Frequent Co-Deletions of CDKN2A and IFN Type I Characterize Malignant Pleural Mesothelioma, Publisher: ELSEVIER SCIENCE INC, Pages: S345-S345, ISSN: 1556-0864
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- Citations: 1
Mandal A, Nastase A, Lu SK, et al., 2019, Analysis of Immune Phenotype Composition in Malignant Pleural Mesothelioma (MPM) Using Bulk RNA Sequencing, Publisher: ELSEVIER SCIENCE INC, Pages: S345-S346, ISSN: 1556-0864
Hoang L, Domingo-Sabugo C, Starren E, et al., 2019, Integrative Omics Analysis Reveals Important Roles of Adenosine Diphosphate in Haemostasis and Platelet Activation in NSCLC, Publisher: ELSEVIER SCIENCE INC, Pages: S419-S419, ISSN: 1556-0864
Wilkinson SL, Edwards M, John S, et al., 2019, Complex indel variant calling in a repetitive genomic region, 52nd Conference of the European-Society-of-Human-Genetics (ESHG), Publisher: NATURE PUBLISHING GROUP, Pages: 1255-1256, ISSN: 1018-4813
Domingo-Sabugo C, Starren E, Mandal A, et al., 2019, Comprehensive Molecular Profiling and Comparison of Common and Rarer Subtypes of Lung Cancer, Publisher: ELSEVIER SCIENCE INC, Pages: S686-S686, ISSN: 1556-0864
Vijayasingam A, Frost E, Wilkins J, et al., 2019, S140 Interim results from a prospective study of tablet and web-based audiometry to detect ototoxicity in adults with cystic fibrosis (vol 73, pg A87, 2018), THORAX, Vol: 74, Pages: 723-723, ISSN: 0040-6376
Wilkinson S, Hodgson U, Honti F, et al., 2019, The application of targeted sequencing and whole exome analysis to identify disease-causing variants in familial pulmonary fibrosis, 51st Conference of the European-Society-of-Human-Genetics (ESHG) in conjunction with the European Meeting on Psychosocial Aspects of Genetics (EMPAG), Publisher: NATURE PUBLISHING GROUP, Pages: 83-84, ISSN: 1018-4813
Edwards M, Wilkinson S, van den Broek F, et al., 2019, Sudden cardiac death caused by bi-allelic variants in the <i>PPA2</i> gene, 51st Conference of the European-Society-of-Human-Genetics (ESHG) in conjunction with the European Meeting on Psychosocial Aspects of Genetics (EMPAG), Publisher: NATURE PUBLISHING GROUP, Pages: 161-161, ISSN: 1018-4813
Budaj I, Gupta P, Saggar A, et al., 2019, IMAGING CARDIOVASCULAR FEATURES OF A FAMILY WITH TYPE 4 LOEYS-DIETZ SYNDROME, Annual Spring Meeting of the British-Society-of-Cardiovascular-Imaging/British-Society-of-Cardiac-Computed-Tomography (BSCI/BSCCT), Publisher: BMJ PUBLISHING GROUP, Pages: A1-A1, ISSN: 1355-6037
Vijayasingam A, Shah A, Simmonds NJ, et al., 2018, INTERIM RESULTS FROM A PROSPECTIVE STUDY OF TABLET AND WEB-BASED AUDIOMETRY TO DETECT OTOTOXICITY IN ADULTS WITH CYSTIC FIBROSIS, THORAX, Vol: 73, Pages: A87-A88, ISSN: 0040-6376
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- Citations: 1
Honti F, Beaman G, Edwards M, et al., 2018, Copy number variants account for at least 2% of non-syndromic cardiomyopathies, 50th European-Society-of-Human-Genetics (ESHG) Conference, Publisher: NATURE PUBLISHING GROUP, Pages: 105-105, ISSN: 1018-4813
Brett L, Wilkinson SL, Monk T, et al., 2018, Mosaicism in inherited cardiac conditions detected by targeted NGS analysis, 50th European-Society-of-Human-Genetics (ESHG) Conference, Publisher: NATURE PUBLISHING GROUP, Pages: 274-275, ISSN: 1018-4813
Hoehe MR, Morris-Rosendahl DJ, 2018, The role of genetics and genomics in clinical psychiatry, Dialogues in Clinical Neuroscience, Vol: 20, Pages: 169-177, ISSN: 1294-8322
The enormous successes in the genetics and genomics of many diseases have provided the basis for the advancement of precision medicine. Thus, the detection of genetic variants associated with neuropsychiatric disorders, as well as treatment outcome, has raised growing expectations that these findings could soon be translated into the clinic to improve diagnosis, the prediction of disease risk and individual response to drug therapy. In this article, we will provide an introduction to the search for genes involved in psychiatric illness and summarize the present findings in major psychiatric disorders. We will review the genetic variants in genes encoding drug metabolizing enzymes and specific drug targets which were found to be associated with variable drug response and severe side effects. We will evaluate the clinical translatability of these findings, whether there is currently any role for genetic testing and in this context, make valuable sources of information available to the clinician seeking guidance and advice in this rapidly developing field of psychiatric genetics.
Whiffin N, walsh R, Govind R, et al., 2018, CardioClassifier: disease- and gene-specific computational decision support for clinical genome interpretation, Genetics in Medicine, Vol: 20, Pages: 1246-1254, ISSN: 1098-3600
PurposeInternationally adopted variant interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) are generic and require disease-specific refinement. Here we developed CardioClassifier (http://www.cardioclassifier.org), a semiautomated decision-support tool for inherited cardiac conditions (ICCs).MethodsCardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation. Combining disease- and gene-specific knowledge with variant observations in large cohorts of cases and controls, we refined 14 computational ACMG criteria and created three ICC-specific rules.ResultsWe benchmarked CardioClassifier on 57 expertly curated variants and show full retrieval of all computational data, concordantly activating 87.3% of rules. A generic annotation tool identified fewer than half as many clinically actionable variants (64/219 vs. 156/219, Fisher’s P = 1.1 × 10−18), with important false positives, illustrating the critical importance of disease and gene-specific annotations. CardioClassifier identified putatively disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with leading ICC laboratories. Through addition of manually curated data, variants found in over 40% of cardiomyopathy cases are fully annotated, without requiring additional user-input data.ConclusionCardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines.
Nastase A, Gennatas S, Mandal A, et al., 2018, Targeted next-generation sequencing of malignant pleural mesothelioma identifies recurrent NRAS oncogene mutations, 16th Annual British Thoracic Oncology Group Conference 2018, Publisher: ELSEVIER IRELAND LTD, Pages: S26-S26, ISSN: 0169-5002
Mandal A, Gennatas S, Liu K, et al., 2018, Copy number variations in malignant pleural mesothelioma reveal novel regions of genomic imbalances, Publisher: ELSEVIER IRELAND LTD, Pages: S27-S27, ISSN: 0169-5002
Zaqout S, Morris-Rosendahl D, Kaindl AM, 2017, Autosomal Recessive Primary Microcephaly (MCPH): An Update, NEUROPEDIATRICS, Vol: 48, Pages: 135-142, ISSN: 0174-304X
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- Citations: 57
von Bohlen AE, Boehm J, Pop R, et al., 2017, A mutation creating an upstream initiation codon in the SOX9 5' UTR causes acampomelic campomelic dysplasia, Molecular Genetics and Genomic Medicine, Vol: 5, Pages: 261-268, ISSN: 2324-9269
BackgroundCampomelic dysplasia (CD) is a semilethal developmental disorder caused by mutations in and around SOX9. CD is characterized by multiple skeletal malformations including bending (campomelia) of long bones. Surviving patients frequently have the acampomelic form of CD (ACD).MethodsThis is a single case report on a patient with clinical and radiological features of ACD who has no mutation in the SOX9 protein-coding sequence nor a translocation with breakpoint in the SOX9 regulatory domain. We include functional studies of the novel mutant protein in vitro and in cultured cells.ResultsThe patient was found to have a de novo heterozygous mutation c.-185G>A in the SOX9 5′UTR. The mutation creates an upstream translation start codon, uAUG, with a much better fit of its flanking sequence to the Kozak consensus than the wild-type AUG. By in vitro transcription-translation and transient transfection into COS-7 cells, we show that the uAUG leads to translation of a short peptide from a reading frame that terminates just after the wild-type AUG start codon. This results in reduced translation of the wild-type protein, compatible with the milder phenotype of the patient.ConclusionFindings support the notion that more mildly affected, surviving CD/ACD patients carry mutant SOX9 alleles with residual expression of SOX9 wild-type protein. Although rarely described in human genetic disease and for the first time here for CD, mutations creating upstream AUG codons may be more common than generally assumed.
Picker-Minh S, Hartenstein S, Proquitte H, et al., 2017, Pontine Tegmental Cap Dysplasia in an Extremely Preterm Infant and Review of the Literature, JOURNAL OF CHILD NEUROLOGY, Vol: 32, Pages: 334-340, ISSN: 0883-0738
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- Citations: 5
Klemann C, Pannicke U, Morris-Rosendahl DJ, et al., 2016, Transplantation from a symptomatic carrier sister restores host defenses but does not prevent colitis in NEMO deficiency., Clinical Immunology, Vol: 164, Pages: 52-56, ISSN: 1521-7035
NF-κB essential modulator (NEMO) deficiency causes ectodermal dysplasia with immunodeficiency in males, while manifesting as incontinentia pigmenti in heterozygous females. We report a family with NEMO deficiency, in which a female carrier displayed skewed X-inactivation favoring the mutant NEMO allele associated with symptoms of Behçet's disease. Hematopoietic stem cell transplantation of an affected boy from this donor reconstituted an immune system with retained skewed X-inactivation. After transplantation no more severe infections occurred, indicating that an active wild-type NEMO allele in only 10% of immune cells restores host defense. Yet he developed inflammatory bowel disease (IBD). While gut infiltrating immune cells stained strongly for nuclear p65 indicating restored NEMO function, this was not the case in intestinal epithelial cells - in contrast to cells from conventional IBD patients. These results extend murine observations that epithelial NEMO-deficiency suffices to cause IBD. High anti-TNF doses controlled the intestinal inflammation and symptoms of Behçet's disease.
Daud S, Kakar N, Goebel I, et al., 2016, Identification of two novel ALS2 mutations in infantile-onset ascending hereditary spastic paraplegia., Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Pages: 1-6, ISSN: 2167-9223
Biallelic mutations of ALS2 cause a clinical spectrum of overlapping autosomal recessive neurodegenerative disorders: infantile-onset ascending hereditary spastic paralysis (IAHSP), juvenile primary lateral sclerosis (JPLS), and juvenile amyotrophic lateral sclerosis (ALS2). We report on eleven individuals affected with IAHSP from two consanguineous Pakistani families. A combination of linkage analysis with homozygosity mapping and targeted sequencing identified two novel ALS2 mutations, a c.194T > C (p.Phe65Ser) missense substitution located in the first RCC-like domain of ALS2/alsin and a c.2998delA (p.Ile1000*) nonsense mutation. This study of extended families including a total of eleven affected individuals suggests that a given ALS2 mutation may lead to a phenotype with remarkable intrafamilial clinical homogeneity.
Erdelyi LS, Mann WA, Morris-Rosendahl DJ, et al., 2015, Mutation in the V2 vasopressin receptor gene, <i>AVPR2</i>, causes nephrogenic syndrome of inappropriate diuresis, KIDNEY INTERNATIONAL, Vol: 88, Pages: 1070-1078, ISSN: 0085-2538
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- Citations: 31
Herbst SM, Proepper CR, Geis T, et al., 2015, LIS1-associated classic lissencephaly: A retrospective, multicenter survey of the epileptogenic phenotype and response to antiepileptic drugs., Brain and Development, ISSN: 1872-7131
BACKGROUND: Patients with LIS1-associated classic lissencephaly typically present with severe psychomotor retardation and drug-resistant epilepsy within the first year. AIM: To analyze the epileptogenic phenotype and response to antiepileptic therapy in LIS1-associated classic lissencephaly. METHOD: Retrospective evaluation of 22 patients (8months-24years) with genetically and radiologically confirmed LIS1-associated classic lissencephaly in 16 study centers. RESULTS: All patients in our cohort developed drug-resistant epilepsy. In 82% onset of seizures was noted within the first six months of life, most frequently with infantile spasms. Later in infancy the epileptogentic phenotype became more variable and included different forms of focal seizures as well generalized as tonic-clonic seizures, with generalized tonic-clonic seizures being the predominant type. Lamotrigine and valproate were rated most successful with good or partial response rates in 88-100% of the patients. Both were evaluated significantly better than levetiracetam (p<0.05) and sulthiame (p<0.01) in the neuropediatric assessment and better than levetiracetam, sulthiame (p<0.05) and topiramate (p<0.01) in the family survey. Phenobarbital and vigabatrin achieved good or partial response in 62-83% of the patients. CONCLUSION: Our findings suggest that patients with LIS1-associated lissencephaly might benefit most from lamotrigine, valproate, vigabatrin or phenobarbital.
Morris-Rosendahl DJ, Kaindl A, 2015, What Next-Generation Sequencing (NGS) technology has enabled us to learn about Primary Autosomal Recessive Microcephaly (MCPH)., Molecular and Cellular Probes, Vol: 29, Pages: 271-281, ISSN: 1096-1194
The impact that next-generation sequencing technology (NGS) is having on many aspects of molecular and cell biology, is becoming increasingly apparent. One of the the most noticeable outcomes of the new technology in human genetics, has been the accelerated rate of identification of disease-causing genes. Especially for rare, heterogeneous disorders, such as autosomal recessive primary microcephaly (MCPH), the handful of genes previously known to harbour disease-causing mutations, has grown at an unprecedented rate within a few years. Knowledge of new genes mutated in MCPH over the last four years has contributed to our understanding of the disorder at both the clinical and cellular levels. The functions of MCPH proteins such as WDR62, CASC5, PHC1, CDK6, CENP-E, CENP-F, CEP63, ZNF335, PLK4 and TUBGPC, have been added to the complex network of critical cellular processes known to be involved in brain growth and size. In addition to the importance of mitotic spindle assembly and structure, centrosome and centriole function and DNA repair and damage response, new mechanisms involving kinetochore-associated proteins and chromatin remodelling complexes have been elucidated. Two of the major contributions to our clinical knowledge are the realisation that primary microcephaly caused by mutations in genes at the MCPH loci is seldom an isolated clinical feature and is often accompanied either by additional cortical malformations or primordial dwarfism. Gene-phenotype correlations are being revisited, with a new dimension of locus heterogeneity and phenotypic variablity being revealed.
Borck G, Hoeg F, Dentici ML, et al., 2015, <i>BRF1</i> mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies (vol 25, pg 155, 2015), GENOME RESEARCH, Vol: 25, Pages: 609-609, ISSN: 1088-9051
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- Citations: 4
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