Articles

Cost-effectiveness analysis of lumacaftor and ivacaftor combination for the treatment of patients with cystic fibrosis in the United States

Lumacaftor/ivacaftor was approved by the Food and Drug Administration (FDA) as a combination treatment for Cystic Fibrosis (CF) patients who are homozygous for the F508del mutation. The objective of this study...

Authors: Dolly Sharma, Shan Xing, Yu-Ting Hung, Rachel N. Caskey, Maria L. Dowell and Daniel R. Touchette

9th European Conference on Rare Diseases & Orphan Products (ECRD Vienna 2018)

Authors:

Broad phenotypic spectrum and genotype-phenotype correlations in GMPPB-related dystroglycanopathies: an Italian cross-sectional study

Dystroglycanopathy (α-DG) is a relatively common, clinically and genetically heterogeneous category of congenital forms of muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD) associated with hyp...

Authors: Guja Astrea, Alessandro Romano, Corrado Angelini, Carlo Giuseppe Antozzi, Rita Barresi, Roberta Battini, Carla Battisti, Enrico Bertini, Claudio Bruno, Denise Cassandrini, Marina Fanin, Fabiana Fattori, Chiara Fiorillo, Renzo Guerrini, Lorenzo Maggi, Eugenio Mercuri…

High hepatic macrophage activation and low liver function in stable Wilson patients - a Danish cross-sectional study

Hepatic macrophage (Kupffer cell) hyperplasia is often described in Wilson’s disease (WD). In many liver diseases, Kupffer cell activation is related to disease severity, liver function, and fibrosis but the i...

Authors: Jessica Björklund, Tea Lund Laursen, Thomas Damgaard Sandahl, Holger Jon Møller, Hendrik Vilstrup, Peter Ott and Henning Grønbæk

Efficacy of sirolimus for the prevention of recurrent pneumothorax in patients with lymphangioleiomyomatosis: a case series

Pneumothorax is one of the most common symptoms in patients with lymphangioleiomyomatosis (LAM). However, current management strategies for patients with LAM who present with recurrent pneumothorax remain inad...

Authors: Li Zhou, Ruoyun Ouyang, Hong Luo, Siying Ren, Ping Chen, Yating Peng, Ting Liu and Guiqian Liu

Molecular and cellular characterizations of human cherubism: disease aggressiveness depends on osteoclast differentiation

Cherubism is a rare autosomal dominant disorder of the jaws caused by mutation of the SH3BP2 gene. The bone is replaced by a fibrous granuloma containing multinucleated giant cells. Cells of the cherubism granulo...

Authors: Natacha Kadlub, Quentin Sessiecq, Marion Mandavit, Aurore Coulomb L’Hermine, Cecile Badoual, Louise Galmiche, Ariane Berdal, Vianney Descroix, Arnaud Picard and Amélie E. Coudert

Fertility in classical galactosaemia, a study of N-glycan, hormonal and inflammatory gene interactions

Classical Galactosaemia (CG) (OMIM #230400) is a rare inborn error of galactose metabolism caused by deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). Long-term complications persist i...

Authors: Hugh-Owen Colhoun, Estela M. Rubio Gozalbo, Annet M. Bosch, Ina Knerr, Charlotte Dawson, Jennifer Brady, Marie Galligan, Karolina Stepien, Roisin O’Flaherty, C. Catherine Moss, P. Peter Barker, Maria Fitzgibbon, Peter P. Doran and Eileen P. Treacy

From motor performance to participation: a quantitative descriptive study in adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a recessive neurological disorder with cerebellar, pyramidal and neuropathic features. Natural history data are urgently needed to increase...

Authors: Cynthia Gagnon, Bernard Brais, Isabelle Lessard, Caroline Lavoie, Isabelle Côté and Jean Mathieu

Systemic retinoids for treatment of recalcitrant IgA pemphigus

IgA pemphigus is an exceedingly rare autoimmune blistering disorder, caused by IgA autoantibodies against desmosomal proteins. No treatment option has been found to be universally effective. The disease is oft...

Authors: Franziska Schauer, Johannes Steffen Kern and Dimitra Kiritsi

Burden of albinism: development and validation of a burden assessment tool

Albinism comprises a group of autosomal recessive diseases that are characterized by poor vision and a variable hypopigmentation phenotype. A comprehensive literature review showed that no tool can assess the ...

Authors: Fanny Morice-Picard, Charles Taïeb, Aurelie Marti, Antoine Gliksohn, Mohammed Bennani, Christine Bodemer and Khaled Ezzedine

Neural stem cells for disease modeling and evaluation of therapeutics for Tay-Sachs disease

Tay-Sachs disease (TSD) is a rare neurodegenerative disorder caused by autosomal recessive mutations in the HEXA gene on chromosome 15 that encodes β-hexosaminidase. Deficiency in HEXA results in accumulation of ...

Authors: Mylinh Vu, Rong Li, Amanda Baskfield, Billy Lu, Atena Farkhondeh, Kirill Gorshkov, Omid Motabar, Jeanette Beers, Guokai Chen, Jizhong Zou, Angela J. Espejo-Mojica, Alexander Rodríguez-López, Carlos J. Alméciga-Díaz, Luis A. Barrera, Xuntian Jiang, Daniel S. Ory…

Description of 22 new alpha-1 antitrypsin genetic variants

Alpha-1 antitrypsin deficiency is an autosomal co-dominant disorder caused by mutations of the highly polymorphic SERPINA1 gene. This genetic disorder still remains largely under-recognized and can be associated ...

Authors: Céline Renoux, Marie-Françoise Odou, Guillaume Tosato, Jordan Teoli, Norman Abbou, Christine Lombard, Farid Zerimech, Nicole Porchet, Colette Chapuis Cellier, Malika Balduyck and Philippe Joly

A continuous repetitive task to detect fatigability in spinal muscular atrophy

To determine the value of a continuous repetitive task to detect and quantify fatigability as additional dimension of impaired motor function in patients with hereditary proximal spinal muscular atrophy (SMA).

Authors: Marloes Stam, Renske I. Wadman, Bart Bartels, Maureen Leeuw, Henk-Jan Westeneng, Camiel A. Wijngaarde, Leonard H. van den Berg and W. Ludo van der Pol

TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study

Most evidence for TSC-associated neuropsychiatric disorders (TAND) to date have come from small studies and case reports, and very little is known about TAND in adults. We explored baseline TAND data from the ...

Authors: Petrus J. de Vries, Elena Belousova, Mirjana P. Benedik, Tom Carter, Vincent Cottin, Paolo Curatolo, Maria Dahlin, Lisa D’Amato, Guillaume B. d’Augères, José C. Ferreira, Martha Feucht, Carla Fladrowski, Christoph Hertzberg, Sergiusz Jozwiak, J. Chris Kingswood, John A. Lawson…

Consensus statement on physical rehabilitation in children and adolescents with osteogenesis imperfecta

On the occasion of the 13th International Conference on Osteogenesis imperfecta in August 2017 an expert panel was convened to develop an international consensus paper regarding physical rehabilitation in chil...

Authors: Brigitte Mueller, Raoul Engelbert, Frances Baratta-Ziska, Bart Bartels, Nicole Blanc, Evelise Brizola, Paolo Fraschini, Claire Hill, Caroline Marr, Lisa Mills, Kathleen Montpetit, Verity Pacey, Miguel Rodriguez Molina, Marleen Schuuring, Chantal Verhille, Olga de Vries…

A health state utility valuation study to assess the impact of treatment mode of administration in Gaucher disease

This study aimed to obtain UK societal-based utility values for health states related to treatment mode of administration using Gaucher disease as the background condition.

Authors: Monica Hadi, Paul Swinburn, Luba Nalysnyk, Alaa Hamed and Atul Mehta

The patient journey to diagnosis and treatment of autoinflammatory diseases

Limited data are available on the experiences of patients with autoinflammatory diseases (AIDs) and their families along the path to diagnosis and treatment. We sought to describe these experiences in patients...

Authors: Jonathan S. Hausmann, Kathleen G. Lomax, Ari Shapiro and Karen Durrant

Rare disease registries: potential applications towards impact on development of new drug treatments

Low prevalence, lack of knowledge about the disease course, and phenotype heterogeneity hamper the development of drugs for rare diseases. Rare disease registries (RDRs) can be helpful by playing a role in und...

Authors: Marijke C. Jansen-van der Weide, Charlotte M. W. Gaasterland, Kit C. B. Roes, Caridad Pontes, Roser Vives, Arantxa Sancho, Stavros Nikolakopoulos, Eric Vermeulen and Johanna H. van der Lee

Eight years after an international workshop on myotonic dystrophy patient registries: case study of a global collaboration for a rare disease

Myotonic Dystrophy is the most common form of muscular dystrophy in adults, affecting an estimated 10 per 100,000 people. It is a multisystemic disorder affecting multiple generations with increasing severity....

Authors: Libby Wood, Guillaume Bassez, Corinne Bleyenheuft, Craig Campbell, Louise Cossette, Aura Cecilia Jimenez-Moreno, Yi Dai, Hugh Dawkins, Jorge Alberto Diaz Manera, Celine Dogan, Rasha el Sherif, Barbara Fossati, Caroline Graham, James Hilbert, Kristinia Kastreva, En Kimura…

Meta-analysis of the clinical and immunopathological characteristics and treatment outcomes in epidermolysis bullosa acquisita patients

Epidermolysis bullosa acquisita (EBA) is an orphan autoimmune disease. Several clinical phenotypes have been described, but subepidermal blistering is characteristic of all variants. Limited data on clinical a...

Authors: Hiroaki Iwata, Artem Vorobyev, Hiroshi Koga, Andreas Recke, Detlef Zillikens, Catherine Prost-Squarcioni, Norito Ishii, Takashi Hashimoto and Ralf J. Ludwig

Manual and educational therapy in the treatment of hemophilic arthropathy of the elbow: a randomized pilot study

Elbow arthropathy is characteristic in patients with hemophilia. Arthropathy is manifested by decreased range of motion, pain, loss of strength and muscular atrophy, and axial changes. The objective is to eval...

Authors: Rubén Cuesta-Barriuso, Antonia Gómez-Conesa and José-Antonio López-Pina

A systematic review of cognitive functioning in early treated adults with phenylketonuria

Even though early dietary management of phenylketonuria (PKU) successfully prevents severe neurological impairments, deficits in cognitive functioning are still observed. These deficits are believed to be the ...

Authors: Denise Leonne Hofman, Claire Louise Champ, Clare Louise Lawton, Mick Henderson and Louise Dye

Cardiac features and effects of enzyme replacement therapy in Taiwanese patients with Mucopolysaccharidosis IVA

Cardiac abnormalities have been observed in patients with mucopolysaccharidosis (MPS) of any type, with the most documented abnormalities being valvular heart disease and cardiac hypertrophy. However, few stud...

Authors: Hsiang-Yu Lin, Ming-Ren Chen, Shan-Miao Lin, Chung-Lieh Hung, Dau-Ming Niu, Chih-Kuang Chuang and Shuan-Pei Lin

Can untreated PKU patients escape from intellectual disability? A systematic review

Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated...

Authors: Danique van Vliet, Annemiek M. J. van Wegberg, Kirsten Ahring, Miroslaw Bik-Multanowski, Nenad Blau, Fatma D. Bulut, Kari Casas, Bozena Didycz, Maja Djordjevic, Antonio Federico, François Feillet, Maria Gizewska, Gwendolyn Gramer, Jozef L. Hertecant, Carla E. M. Hollak, Jens V. Jørgensen…

Healthcare burden of rare diseases in Hong Kong – adopting ORPHAcodes in ICD-10 based healthcare administrative datasets

The burden of rare diseases is important for healthcare planning but difficult to estimate. This has been facilitated by the development of ORPHAcodes, a comprehensive classification and coding system for rare...

Authors: Annie Ting Gee Chiu, Claudia Ching Yan Chung, Wilfred Hing Sang Wong, So Lun Lee and Brian Hon Yin Chung

Profiling of intracellular metabolites produced from galactose and its potential for galactosemia research

Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible t...

Authors: Michel van Weeghel, Lindsey Welling, Eileen P. Treacy, Ronald J. A. Wanders, Sacha Ferdinandusse and Annet M. Bosch

Dentinogenesis imperfecta type II in Swedish children and adolescents

Dentinogenesis imperfecta (DGI) is a heritable disorder of dentin. Genetic analyses have found two subgroups in this disorder: DGI type I, a syndromic form associated with osteogenesis imperfecta (OI), and DGI...

Authors: K. Andersson, B. Malmgren, E. Åström and G. Dahllöf

A randomized placebo controlled clinical trial to evaluate the efficacy and safety of minocycline in patients with Angelman syndrome (A-MANECE study)

Minocycline is an old tetracycline antibiotic that has shown antiinflammatory and antiapoptotic properties in different neurological disease mouse models. Previous single arm study in humans demonstrated benef...

Authors: Belén Ruiz-Antoran, Aranzazu Sancho-López, Rosario Cazorla-Calleja, Luis Fernando López-Pájaro, Ágata Leiva, Gema Iglesias-Escalera, Maria Esperanza Marín-Serrano, Marta Rincón-Ortega, Julián Lara-Herguedas, Teresa Rossignoli-Palomeque, Sara Valiente-Rodríguez, Javier González-Marques, Enriqueta Román-Riechmann and Cristina Avendaño-Solá

Diagnostics of rare disorders: whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders

The telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKC), the clinical features of TBDs ste...

Authors: Luca Trotta, Anna Norberg, Mervi Taskinen, Vivien Béziat, Sofie Degerman, Ulla Wartiovaara-Kautto, Hannamari Välimaa, Kirsi Jahnukainen, Jean-Laurent Casanova, Mikko Seppänen, Janna Saarela, Minna Koskenvuo and Timi Martelius

Encephalopathies with intracranial calcification in children: clinical and genetic characterization

We present a group of patients affected by a paediatric onset genetic encephalopathy with cerebral calcification of unknown aetiology studied with Next Generation Sequencing (NGS) genetic analyses.

Authors: Davide Tonduti, Celeste Panteghini, Anna Pichiecchio, Alice Decio, Miryam Carecchio, Chiara Reale, Isabella Moroni, Nardo Nardocci, Jaume Campistol, Angela Garcia-Cazorla, Belen Perez Duenas, Luisa Chiapparini, Barbara Garavaglia and Simona Orcesi

Research, diagnosis and education in inborn errors of metabolism in Colombia: 20 years’ experience from a reference center

The use of specialized centers has been the main alternative for an appropriate diagnosis, management and follow up of patients affected by inborn errors of metabolism (IEM). These centers facilitate the train...

Authors: Olga Y. Echeverri, Johana M. Guevara, Ángela J. Espejo-Mojica, Andrea Ardila, Ninna Pulido, Magda Reyes, Alexander Rodriguez-Lopez, Carlos J. Alméciga-Díaz and Luis A. Barrera

Annual severity increment score as a tool for stratifying patients with Niemann-Pick disease type C and for recruitment to clinical trials

Niemann-Pick disease type C (NPC) is a lysosomal storage disease with a heterogeneous neurodegenerative clinical course. Multiple therapies are in clinical trials and inclusion criteria are currently mainly ba...

Authors: Mario Cortina-Borja, Danielle te Vruchte, Eugen Mengel, Yasmin Amraoui, Jackie Imrie, Simon A. Jones, Christine i Dali, Paul Fineran, Thomas Kirkegaard, Heiko Runz, Robin Lachmann, Tatiana Bremova-Ertl, Michael Strupp and Frances M. Platt

Healthcare resource utilization in the management of hypophosphatasia in three patients displaying a spectrum of manifestations

Hypophosphatasia (HPP) is a rare, heterogeneous disease caused by low tissue-nonspecific alkaline phosphatase activity and associated with a range of signs and symptoms, including bone mineralization defects, ...

Authors: Anjali B. Daniel, Vrinda Saraff, Nick J. Shaw, Robert Yates, M. Zulf Mughal and Raja Padidela

Miglustat in Niemann-Pick disease type C patients: a review

Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive, neurodegenerative disease associated with a wide variety of progressive neurological manifestations. Miglustat is indicated for the treatment ...

Authors: Mercè Pineda, Mark Walterfang and Marc C. Patterson

Missense mutation in SLIT2 associated with congenital myopia, anisometropia, connective tissue abnormalities, and obesity

SLIT2 is a protein ligand for the Roundabout (ROBO) receptor and was found to play a major role in repulsive midline axon guidance in central nervous system development. Based on studies utilizing knockout mod...

Authors: Katherine Y. Liu, Jesse D. Sengillo, Gabriel Velez, Ruben Jauregui, Lynn Y. Sakai, Irene H. Maumenee, Alexander G. Bassuk, Vinit B. Mahajan and Stephen H. Tsang

Characterization of vertigo and hearing loss in patients with Fabry disease

Fabry Disease (FD) is an X-linked hereditary lysosomal storage disorder which leads to a multisystemic intralysosomal accumulation of globotriaosylceramid (Gb3). Besides prominent renal and cardiac organ invol...

Authors: Maria Köping, Wafaa Shehata-Dieler, Dieter Schneider, Mario Cebulla, Daniel Oder, Jonas Müntze, Peter Nordbeck, Christoph Wanner, Rudolf Hagen and Sebastian P. Schraven

European Reference Network For Rare Vascular Diseases (VASCERN) Outcome Measures For Hereditary Haemorrhagic Telangiectasia (HHT)

Hereditary haemorrhagic telangiectasia (HHT) is a multisystemic vascular dysplasia that leads to nosebleeds, anaemia due to blood loss, and arteriovenous malformations (AVMs) in organs such as the lungs, liver...

Authors: Claire L. Shovlin, Elisabetta Buscarini, Anette D. Kjeldsen, Hans Jurgen Mager, Carlo Sabba, Freya Droege, Urban Geisthoff, Sara Ugolini and Sophie Dupuis-Girod

The clinical spectrum and genetic variability of limb-girdle muscular dystrophy in a cohort of Chinese patients

Limb-girdle muscular dystrophy (LGMD) is a commonly diagnosed hereditary muscular disorder, characterized by the progressive weakness of the limb-girdle muscles. Although the condition has been well-characteri...

Authors: Liang Wang, Victor Wei Zhang, Shaoyuan Li, Huan Li, Yiming Sun, Jing Li, Yuling Zhu, Ruojie He, Jinfu Lin and Cheng Zhang

The efficacy and adverse events of mTOR inhibitors in lymphangioleiomyomatosis: systematic review and meta-analysis

Lymphangioleiomyomatosis (LAM) is a rare lung disease and the mammalian target of the rapamycin (mTOR) inhibitors has been used as an effective therapy. Here we conducted a systematic review and meta-analysis ...

Authors: Nannan Gao, Tengyue Zhang, Jiadong Ji, Kai-Feng Xu and Xinlun Tian

A prospective natural history study of Krabbe disease in a patient cohort with onset between 6 months and 3 years of life

Krabbe disease is a rare neurodegenerative disorder caused by a deficiency in the lysosomal enzyme galactocerebrosidase. Patients with Krabbe disease present with a variable disease course depending on their a...

Authors: Nicholas Bascou, Anthony DeRenzo, Michele D. Poe and Maria L. Escolar

Craniofacial and oral alterations in patients with Neurofibromatosis 1

Neurofibromatosis type 1 (NF1) is one of the most common inherited syndromes. The literature on craniofacial alterations associated with NF1 has been limited and partially contradictory. This review is based o...

Authors: Vivian Visnapuu, Sirkku Peltonen, Lotta Alivuotila, Risto-Pekka Happonen and Juha Peltonen

Health-related quality of life in children with PFAPA syndrome

Conventionally, PFAPA syndrome is considered as a benign disease compared to other recurrent fevers because it completely passes before adulthood. However, in our clinical practice, fever episodes have a huge ...

Authors: Claire Grimwood, Isabelle Kone-Paut, Maryam Piram, Linda Rossi-Semerano and Véronique Hentgen

Clinical presentation and outcome in infantile Sandhoff disease: a case series of 25 patients from Iranian neurometabolic bioregistry with five novel mutations

Infantile Sandhoff disease (ISD) is a GM2 gangliosidosis that is classified as a lysosomal storage disorder. The most common symptoms of affected individuals at presentation are neurologic involvement. Here we...

Authors: Ali Reza Tavasoli, Nima Parvaneh, Mahmoud Reza Ashrafi, Zahra Rezaei, Johannes Zschocke and Parastoo Rostami

Deep characterization of the anti-drug antibodies developed in Fabry disease patients, a prospective analysis from the French multicenter cohort FFABRY

Fabry disease (OMIM #301500) is an X-linked disorder caused by alpha-galactosidase A deficiency with two major clinical phenotypes: classic and non-classic of different prognosis. From 2001, enzyme replacement...

Authors: Wladimir Mauhin, Olivier Lidove, Damien Amelin, Foudil Lamari, Catherine Caillaud, Federico Mingozzi, Gaëlle Dzangué-Tchoupou, Louiza Arouche-Delaperche, Claire Douillard, Bertrand Dussol, Vanessa Leguy-Seguin, Pauline D’Halluin, Esther Noel, Thierry Zenone, Marie Matignon, François Maillot…

Key issues in Rett syndrome: emotional, behavioural and autonomic dysregulation (EBAD) - a target for clinical trials

Complex neurodevelopmental disorders need multi-disciplinary treatment approaches for optimal care. The clinical effectiveness of treatments is limited in patients with rare genetic syndromes with multisystem ...

Authors: Jatinder Singh and Paramala Santosh

Prevalence and healthcare burden of pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare syndrome of alveolar surfactant accumulation, resulting hypoxemic respiratory failure, and increased infection risk. Despite advances in our understanding of dise...

Authors: Cormac McCarthy, Ruzan Avetisyan, Brenna C. Carey, Claudia Chalk and Bruce C. Trapnell

Improving the diagnosis of cobalamin and related defects by genomic analysis, plus functional and structural assessment of novel variants

Cellular cobalamin defects are a locus and allelic heterogeneous disorder. The gold standard for coming to genetic diagnoses of cobalamin defects has for some time been gene-by-gene Sanger sequencing of indivi...

Authors: Sandra Brasil, Fátima Leal, Ana Vega, Rosa Navarrete, María Jesús Ecay, Lourdes R. Desviat, Casandra Riera, Natàlia Padilla, Xavier de la Cruz, Mari Luz Couce, Elena Martin-Hernández, Ana Morais, Consuelo Pedrón, Luis Peña-Quintana, Miriam Rigoldi, Norma Specola…

The burden of congenital hyperinsulinism in the United Kingdom: a cost of illness study

Congenital hyperinsulinism (CHI) is a rare, genetic disease which causes persistent hypoglycaemia, typically in new-borns. Patients with the diffuse disease variant often require near-total surgical removal of...

Authors: Sana Eljamel, Annabel Griffiths, Jenni Evans, Indraneel Banerjee, Khalid Hussain and Richard Thompson

ROHHAD and Prader-Willi syndrome (PWS): clinical and genetic comparison

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a very rare and potentially fatal pediatric disorder, the cause of which is presently unknown. ROHHAD...

Authors: Sarah F. Barclay, Casey M. Rand, Lisa Nguyen, Richard J. A. Wilson, Rachel Wevrick, William T. Gibson, N. Torben Bech-Hansen and Debra E. Weese-Mayer

Fatal pitfalls in newborn screening for mitochondrial trifunctional protein (MTP)/long-chain 3-Hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency

Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency are long-chain fatty acid oxidation disorders with particularly high morbidity and mortality. Outcome...

Authors: Amelie S. Lotz-Havla, Wulf Röschinger, Katharina Schiergens, Katharina Singer, Daniela Karall, Vassiliki Konstantopoulou, Saskia B. Wortmann and Esther M. Maier