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Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies
A. Lischka, K. Eggermann, CJ. Record, MF. Dohrn, P. Laššuthová, F. Kraft, M. Begemann, D. Dey, T. Eggermann, D. Beijer, J. Šoukalová, M. Laura, AM. Rossor, R. Mazanec, J. Van Lent, PJ. Tomaselli, M. Ungelenk, KY. Debus, SME. Feely, D. Gläser, S....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
Grantová podpora
Swiss National Science Foundation - Switzerland
21950
Versus Arthritis - United Kingdom
MR/R011737/1
Medical Research Council - United Kingdom
MR/W002388/1
Versus Arthritis - United Kingdom
200183/Z/15/Z
Wellcome Trust - United Kingdom
Wellcome Trust - United Kingdom
NLK
Free Medical Journals
od 1996 do Před 1 rokem
Open Access Digital Library
od 1996-01-01
PubMed
37769650
DOI
10.1093/brain/awad328
Knihovny.cz E-zdroje
- MeSH
- dědičné senzorické a autonomní neuropatie * genetika MeSH
- kongenitální analgezie * genetika MeSH
- lidé MeSH
- mutace genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies.
Center for Human Genetics Genetikum® 89231 Neu Ulm Germany
Centre for Medical Genetics Universitair Ziekenhuis Brussel 1090 Jette Brussels Belgium
Davis and Davis Children's Hospital University of California Sacramento CA 95817 USA
Department of Genetics Hospital Infantil Doutor Juvêncio Mattos São Luis Maranhão 65015 460 Brazil
Department of Medical Genetics University Hospital Brno 625 00 Brno Czechia
Department of Neurology Medical Faculty of the RWTH Aachen University 52074 Aachen Germany
Department of Neurology University of Iowa Carver College of Medicine Iowa City IA 52242 USA
Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London WC1N 3BG UK
Department of Orthopedics and Trauma Surgery Medical University of Vienna 1090 Vienna Austria
Department of Pediatrics Government Medical College Kozhikode Kerala 673 008 India
Department of Pedodontics Faculty of Dentistry Dicle University 21200 Diyarbakir Turkey
Genetics Department Sorbonne Université Paris Brain Institute APHP INSERM CNRS 75013 Paris France
Genomics Group Institute of Biomedical and Genetic Engineering Islamabad 44000 Pakistan
INSERM MMG U 1251 Marseille France Aix Marseille Univ 13385 Marseille France
Institute for Paramedical Sciences Khyber Medical University Peshawar KPK 25100 Pakistan
Institute of Human Genetics School of Medicine Technical University of Munich 81675 Munich Germany
Institute of Human Genetics University Hospital Jena 07747 Jena Germany
Institute of Medical Genetics and Applied Genomics University of Tübingen 72076 Tübingen Germany
Institute of Neurophysiology Medical Faculty Uniklinik RWTH Aachen University 52074 Aachen Germany
MVZ Humangenetik Bremen Limbach Genetics 28209 Bremen Germany
Neurologie Praxis für Neurologie und Schlafmedizin 53359 Rheinbach Germany
Nuffield Department of Clinical Neuroscience University of Oxford Oxford OX3 9DU UK
Pediatría Clínica Premium 29601 Marbella Spain
Pediatric Neurology and Neurodevelopment Medanta The Medicity Gurgaon Haryana 122 001 India
Pediatric Neurology Children's Hospital of the King's Daughters in Norfolk Norfolk VA 23507 USA
Citace poskytuje Crossref.org
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