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Scientific Publications

Curious About the Latest Scientific Discoveries?

Allgrove Syndrome with Neurological Symptoms

We report a young woman with the clinical picture of Allgrove syndrome in whom neurological symptoms are prominent. It usually presents in the first decade of life with a deficiency of tears, recurrent vomiting and dysphagia due to achalasia.

We report a young woman with the clinical picture of Allgrove syndrome in whom neurological symptoms are prominent. It usually presents in the first decade of life with a deficiency of tears, recurrent vomiting and dysphagia due to achalasia, severe hypoglycemic seizures and shock due to adrenal insufficiency.

EndocrinologyNephrologyNeurology
Author(s): Jerie, M
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GRIN2B Encephalopathy: Novel Findings

We found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment and MCD. Read more!

We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research cohorts, as well as from 43 patients from the literature. Functional consequences and response to memantine treatment were investigated in vitro and eventually translated into patient care. In addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment and MCD revealing novel phenotypic consequences of channelopathies.

Neurology
Author(s): Rolfs, Prof. Arndt, MD, Jamra, Rami Abou, MD, Platzer, Konrad, MD, Yuan, Hongjie, PhD, MD, Schütz, Hannah, Winschel, Alexander, Chen, Wenjuan, Hu, Chun, Kusumoto, Hirofumi, Heyne, Henrike, MD, Helbig, Katherine, Tang, Sha, PhD, Willing, Marcia, PhD, MD, Tinkle, Brad, PhD, MD, Adams, Darius, MD, Depienne, Christel, PhD, Keren, Boris, PhD, MD, Mignot, Cyril, PhD, MD, Frengen, Prof. Eirik, PhD, Strømme, Prof. Petter, PhD, Biskup, Saskia, PhD, MD, Döcker, Dennis, MD, Strom, Tim, MD, Mefford, Heather, PhD, MD, Myers, Candace, PhD, Muir, Alison, PhD, LaCroix, Amy, Sadleir, Lynette, MD, Scheffer, Ingrid, PhD, Brilstra, Eva, PhD, MD, van Haelst, Mieke, MD, van der Smagt, Jasper, MD, Bok, Levinus, MD, Møller, Rikke, Jensen, Prof. Uffe, PhD, MD, Millichap, John, MD, Berg, Anne, PhD, Goldberg, Ethan, PhD, MD, De Bie, Isabelle, PhD, MD, Fox, Stephanie, Major, Philippe, MD, Jones, Julie, PhD, Zackai, Elaine, MD, Leventer, Richard, PhD, Lawson, John Anthony, PhD, Roscioli, Tony, PhD, Jansen, Floor, PhD, MD, Ranza, Emmanuelle, MD, Korff, Christian, MD, Lehesjoki, Anna-Elina, PhD, MD, Courage, Carolina, MD, Linnankivi, Tarja, PhD, MD, Smith, Douglas, PhD, Stanley, Christine, PhD, Mintz, Mark, MD, McKnight, Dianalee, PhD, Decker, Amy, Tan, Wen-Hann, MD, Tarnopolsky, Mark, PhD, MD, Brady, Lauren, Wolff, Markus, MD, Dondit, Lutz, MD, Pedro, Helio, MD, Parisotto, Sarah, Jones, Kelly, MD, Patel, Anup, MD, Franz, David, MD, Vanzo, Rena, Marco, Elysa, MD, Ranells, Judith, MD, Di Donato, Nataliya, MD, Dobyns, William, MD, Laube, Prof. Bodo, PhD, Traynelis, Stephen, PhD, Lemke, Prof. Johannes, MD
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Identification of a Novel GLA Gene Mutation, p.Ile239Met, in Fabry Disease With a Predominant Cardiac Phenotype

Here we report a novel GLA mutation, p.Ile239Met, identified in a large Hungarian three-generation family with FD. Read more in our latest scientific article!

Fabry disease (FD) is an X-linked inherited lysosomal storage disorder caused by mutations in the GLA gene, encoding for the enzyme α-galactosidase A. Although hundreds of mutations in the GLA gene have been described, many of them are variants of unknown significance. Here we report a novel GLA mutation, p.Ile239Met, identified in a large Hungarian three-generation family with FD. We conclude that the p.Ile239Met GLA mutation is a pathogenic mutation for FD associated with predominant cardiac phenotype.

BiomarkerMetabolic Disorders
Author(s): Rolfs, Prof. Arndt, MD, Eichler, Sabrina, PhD, Csanyi, Beata, PhD, Hategan, Lidia, PhD, Nagy, Viktória, MD, Obál, Izabella, PhD, Varga, Edina T., PhD, Borbás, János, MD, Tringer, Annamária, MD, Forster, Tamás, DSc, Sepp, Róbert, MD
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Homozygous p.(Glu87Lys) Variant in ISCA1

The iron-sulfur (Fe-S) cluster (ISC) biogenesis pathway is indispensable for many fundamental biological processes and pathogenic variations in genes encoding several components of the Fe-S biogenesis machinery, such as NFU1, BOLA3, IBA57 and ISCA2.

The iron-sulfur (Fe-S) cluster (ISC) biogenesis pathway is indispensable for many fundamental biological processes and pathogenic variations in genes encoding several components of the Fe-S biogenesis machinery, such as NFU1, BOLA3, IBA57 and ISCA2 are already implicated in causing four types of multiple mitochondrial dysfunctions syndromes (MMDS).

Neurology
Author(s): Shukla, Anju, MD
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The Hidden Niemann-Pick Type C Patient

Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations.

Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields.

BiomarkerMetabolic Disorders
Author(s): Hendriksz, Christian J., MD
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Evidence for Inflammation in Fabry’s Disease? Headache and Muscle Involvement Responding to Corticosteroid and Methotrexate Treatment

In addition to the deposition of lyso-gb3 secondary inflammatory mechanisms may play an important role in the pathophysiology of symptoms in Fabry’s disease. Read more!

We report the case of a 38-year-old female patient who had been diagnosed as lupus erythematosus because of generalized muscle and burning pain combined with slightly elevated C-reactive protein (CRP) and antinuclear antibodies (ANA) 1:640. Twelve years later, Fabry’s disease was diagnosed by molecular genetics. Lupus erythematosus and any other co-morbid rheumatologic diseases were falsified retrospectively and prospectively according to international classification criteria. This case illustrates, that in addition to the deposition of lyso-gb3 secondary inflammatory mechanisms may play an important role in the pathophysiology of symptoms in Fabry’s disease.

BiomarkerNeurology
Author(s): Rolfs, Prof. Arndt, MD, Karabul, Nesrin, MD, Kraemer, Markus, MD, Berlit, Prof. Peter, MD
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Posterior versus Anterior Circulation Stroke in Young Adults: A Comparative Study of Stroke Aetiologies and Risk Factors in Stroke among Young Fabry Patients

Our data suggested a different pattern of aetiology and risk factors in young patients with PCS compared to those with ACS. Read more in our latest publication!

Although 20–30% of all strokes occur in the posterior circulation, few studies have explored the characteristics of patients with strokes in the posterior compared to the anterior circulation so far. Especially data on young patients is missing. In this secondary analysis of data of the prospective multi-centre European sifap1 study that investigated stroke and transient ischemic attack (TIA) patients aged 18–55 years, we compared vascular risk factors, stroke aetiology, presence of white matter hyperintensities (WMH) and cerebral microbleeds (CMB) between patients with ischaemic posterior circulation stroke (PCS) and those having suffered from anterior circulation stroke (ACS) based on cerebral MRI.

CardiovascularNeurology
Author(s): Rolfs, Prof. Arndt, MD, Tanislav, Prof. Christian, MD, Grittner, Ulrike, PhD, Enzinger, Christian, MD, von Sarnowski, Bettina, MD, Putaala, Prof. Jukka, Kaps, Prof. Manfred, MD, Tatlisumak, Turgut, Fazekas, Prof. Franz, MD, Böttcher, Tobias, PhD, Schminke, Prof. Ulf, MD, Hennerici, Prof. Michael, MD, Kessler, Prof. Christof, MD
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Novel GNB1 Mutations Disrupt Assembly and Function of G Protein Heterotrimers and Cause Global Developmental Delay in Humans

Using exome sequencing, we identified 14 different novel variants in GNB1 in 16 pediatric patients. Read more in our latest scientific articles!

Global developmental delay (GDD), often accompanied by intellectual disability, seizures and other features is a severe, clinically and genetically highly heterogeneous childhood-onset disorder. In cases where genetic causes have been identified, de-novo mutations in neuronally expressed genes are a common scenario. These mutations can be best identified by exome sequencing of parent-offspring trios. De novo mutations in the guanine nucleotide-binding protein, beta 1 (GNB1) gene, encoding the Gβ1 subunit of heterotrimeric G proteins, have recently been identified as a novel genetic cause of GDD.

NeurologyWES
Author(s): Rolfs, Prof. Arndt, MD, Klein, Prof. Christine, MD, Trujillano, Daniel, PhD, Lohmann, Katja, PhD, Oprea, Gabriela-Elena, PhD, Steinrücke, Sofia, Münchau, Alexander, MD, Masuho, Ikuo, PhD, Patil, Dipak N., PhD, Baumann, Hauke, Hebert, Eva, Skamangas, Nickolas K., Dobricic, Valerija, PhD, Hüning, Irina, MD, Gillessen-Kaesbach, Prof. Gabriele, MD, Westenberger, Ana, PhD, Savic-Pavicevic, Dusanka, PhD, Martemyanov, Kirill A., PhD
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Clinical Exome Sequencing – Results from 2819 Samples Reflecting 1000 Families

A study was conducted using WES to identify underlying pathogenic variants, or likely pathogenic variants, in 1,000 diagnostic cases from 54 different countries. Read more!

A study was conducted using whole exome sequencing (WES) to identify underlying pathogenic variants, or likely pathogenic variants, in 1,000 diagnostic cases from 54 different countries. Patients selected displayed a wide variety in the number, nature and severity of symptoms. Clinical information given by the requesting physicians was translated to HPO terms and WES was performed on patient samples according to standardized settings.

BiodatabankNGSWES
Author(s): Rolfs, Prof. Arndt, MD, Alfadhel, Majid, MD, Jamra, Rami Abou, MD, Bertoli-Avella, Aida M., MD, Trujillano, Daniel, PhD, Brandau, Oliver, MD, Kandaswamy, Krishna Kumar, PhD, Nahavandi, Nahid, Weiss, Maximilian E. R., Köster, Julia, Werber, Martin, Alrifai, Muhammad Talal, Al Othaim, Ali, Eyaid, Wafaa, Paknia, Omid, PhD, Schröder, Rolf, Garcia-Aznar, Jose Maria, Calvo del Castillo, Maria, PhD, Baldi, Caterina, PhD, Wessel, Karen, PhD, Kishore, Shivendra, PhD, Al-Rumayyan, Ahmed, MD, Al-Twaijri, Waleed, Al Hashem, Amal, Al-Sannaa, Nouriya, Al-Balwi, Mohammed
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Global Genotype–Phenotype Database for Rare Diseases

In this publication we introduce a comprehensive and global genotype–phenotype database focusing on rare diseases. Read more!

“The ability to discover genetic variants in a patient runs far ahead of the ability to interpret them. Databases with accurate descriptions of the causal relationship between the variants and the phenotype are valuable since these are critical tools in clinical genetic diagnostics. Here, we introduce a comprehensive and global genotype–phenotype database focusing on rare diseases.”

BiodatabankNGSWGS
Author(s): Rolfs, Prof. Arndt, MD, Jamra, Rami Abou, MD, Bertoli-Avella, Aida M., MD, Trujillano, Daniel, PhD, Oprea, Gabriela-Elena, PhD, Schmitz, Yvonne, PhD
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Guidelines for Diagnostic Next-Generation Sequencing

Here we present guidelines for the evaluation and validation of next-generation sequencing applications for the diagnosis of genetic disorders. Read more!

The work was performed by a group of laboratory geneticists and bioinformaticians, and discussed with clinical geneticists, industry and patients’ representatives, and other stakeholders in the field of human genetics. The statements that were written during the elaboration of the guidelines are presented here.

NGSWESWGS
Author(s): Bauer, Dr. Peter, MD, Matthijs, Gert, PhD, Souche, Erika, PhD, Alders, Mariëlle, PhD, Corveleyn, Anniek, Eck, Sebastian, Feenstra, Ilse, PhD, Race, Valérie, Sistermans, Erik, PhD, Sturm, Marc, PhD, Weiss, Marjan, PhD, Yntema, Helger, PhD, Bakker, Egbert, PhD, Scheffer, Hans, PhD
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Novel GNB1 Missense Mutation in a Patient with Generalized Dystonia, Hypotonia, and Intellectual Disability

Exome sequencing of a 15-year-old German girl and her unaffected parents revealed a heterozygous heterozygous de novo mutation in GNB1. Read more!

Recently, exome sequencing has extended our knowledge of genetic causes of developmental delay through identification of de novo, germline mutations in the guanine nucleotide-binding protein, beta 1 (GNB1) in 13 patients with neurodevelopmental disability and a wide range of additional symptoms and signs including hypotonia in 11 and seizures in 10 of the patients. Limb/arm dystonia was found in 2 patients.

NeurologyWES
Author(s): Rolfs, Prof. Arndt, MD, Lohmann, Katja, PhD, Steinrücke, Sofia, Domingo, Aloysius, MD, Bäumer, Tobias, MD, Spiegler, Juliane, MD, Hartmann, Corinna, MD, Münchau, Alexander, MD
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Identification of a Novel Deletion in the MMAA Gene in Two Iranian Siblings with Vitamin B12-Responsive Methylmalonic Acidemia

We demonstrate that the deletion in exon 4 of the MMAA gene is a pathogenic allele via a nucleotide frame shift. Read more!

Adenosylcobalamin (vitamin B12) is a coenzyme required for the activity of methylmalonyl-CoA mutase. Defects in this enzyme are a cause of methylmalonic acidemia (MMA). Methylmalonic acidemia, cblA type, is an inborn error of vitamin B12 metabolism that occurs due to mutations in the MMAA gene. MMAA encodes the enzyme which is involved in translocation of cobalamin into the mitochondria.

BiomarkerMetabolic Disorders
Author(s): Rolfs, Prof. Arndt, MD, Keyfi, F., Moghaddassian, Morteza, Varasteh, Prof. Abdol Reza, MD, Abbaszadegan, Mohammad Reza, PhD, Orolicki, Slobodanka, MD PhD
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Robustness of Comprehensive DNA- and RNA-Based Assays at Diagnosis of Acute Myeloid Leukemia Using Blood and Bone Marrow Stored on Filter Cards

In this study, we performed a comparison of cytogenetics, FISH and molecular diagnostic assays based on standard liquid peripheral blood or bone marrow samples and on diagnostic material stored on filter cards. Read more!

“Molecular analyses in hematologic malignancies gained considerable importance in the last decade at diagnosis and for minimal residual disease (MRD). In our study, we performed a comparison of state-of-the-art cytogenetics, FISH and molecular diagnostic assays based on standard liquid peripheral blood or bone marrow samples and on diagnostic material stored on filter cards.”

CentoCard®HematologyOncology
Author(s): Haferlach, Prof. Thorsten, PhD MD, Weber, Simone, Konietschke, Rabea, Nadarajah, Niroshan, Stengel, Anna, PhD, Kern, Wolfgang, MD, Haferlach, Claudia, MD, Meggendorfer, Manja, PhD
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Multicenter Female Fabry Study (MFFS)

The aim of this study was to assess manifestations of and applied treatment concepts for females with Fabry disease according to the current European Guidelines. Read more!

The aim of the present study was to assess manifestations of and applied treatment concepts for females with Fabry disease (FD) according to the current European Fabry Guidelines. Between 10/2008 and 12/2014, data from the most recent visit of 261 adult female FD patients from six German Fabry centers were retrospectively analyzed. Clinical presentation and laboratory data, including plasma lyso-Gb3 levels were assessed.

BiomarkerMetabolic Disorders
Author(s): Rolfs, Prof. Arndt, MD, Giese, Anne Katrin, MD, Wanner, Christoph, MD, Weidemann, Frank, MD, Duning, Prof. Thomas, MD, Lenders, Malte, PhD, Hennermann, Prof. Julia B., MD, Kurschat, Christine Elisabeth, MD, Canaan-Kühl, Sima, MD, Sommer, Prof. Claudia, MD, Üçeyler, Prof. Nurcan, MD, Kampmann, Christopf, MD PhD, Karabul, Nesrin, MD, Stypmann, Prof. Jörg, MD, Krämer, Johannes, MD, Brand, Prof. Stefan-Martin, MD PhD, Brand, Prof. Eva, MD PhD
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