ArticleCell reports2015
Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy.
Open access · goldAbstract read
In one paragraph
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
165citing papers in PubMed, 1 pooled it
11.6field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
165 citing papers in PubMed, 1 synthesis or guideline pooled it, 244 citations in OpenAlex.
- Current profile of Charcot-Marie-Tooth disease in Africa: A systematic review.Journal of the peripheral nervous system : JPNS · 2022Pooled it
- Molecular etiology of arthrogryposis in multiple families of mostly Turkish origin.The Journal of clinical investigation · 2016Trial
- Optical genome mapping improves structural variant detection and characterization in syndromic and neurogenetic disorders.Human genetics · 2026Article
- Tyrosine Supplementation Rescues a Growth Defect in a HumanizedInternational journal of molecular sciences · 2026Article
- Peripheral Myelin Protein-22 and Its Prominence in Charcot-Marie-Tooth Disease.Chemical reviews · 2026Review
- Replating Induces mTOR-Dependent Rescue of Protein Synthesis in Charcot-Marie-Tooth Diseased Neurons.eNeuro · 2026Article
- PathogenicHuman mutation · 2026Article
- Mathematical Model to Assess Mutational Burden in Retinal Dystrophy Patients Negative to Mendelian Genetic Tests and Carriers of Multiple Recessive Variants.Journal of ophthalmic & vision research · 2026Article
- Parallel and non-parallel features of adaptive radiation in Yucatán pupfishes.bioRxiv : the preprint server for biology · 2025Article
- Search for Additional Pathogenic Variants to Explain Variation inNeurology. Genetics · 2025Article
- Oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling and therapeutic implications.Journal of neurology, neurosurgery, and psychiatry · 2025Article
- Molecular genetics of J-domain protein-related chaperonopathies in skeletal muscle.Journal of human genetics · 2025Review
- High-Fat Diet Disrupt Nerve Function by Targeting Schwann Cells.Journal of the peripheral nervous system : JPNS · 2025Article
- Impaired DNAJB2 Response to Heat Shock in Fibroblasts from a Neuropathy Patient withNeurology international · 2025Article
- Yeast models for Charcot-Marie-Tooth disease-causing aminoacyl-tRNA synthetase alleles reveal the cellular basis of disease.IUBMB life · 2025Review
- Modeling of Charcot-Marie-Tooth disease in zebrafish.Frontiers in molecular neuroscience · 2025Review
- Article
- Expanding the genetic spectrum of hereditary motor sensory neuropathies in Pakistan.BMC neurology · 2024Article
- Two novel DnaJ chaperone proteins CG5001 and P58IPK regulate the pathogenicity of Huntington's disease related aggregates.Scientific reports · 2024Article
- Impacts of Elevated COPlants (Basel, Switzerland) · 2024Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors at 12 institutions in 3 countries.
Claudia Gonzaga-JaureguiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Center for Human Disease Modeling, Duke University, Durham, NC 27701, USA.
Tamar HarelDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Tomasz GambinDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Maria KousiCenter for Human Disease Modeling, Duke University, Durham, NC 27701, USA.
Laurie B GriffinCellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Ludmila FrancescattoCenter for Human Disease Modeling, Duke University, Durham, NC 27701, USA.
Burcak OzesDepartment of Molecular Biology and Genetics, Bogazici University, Istanbul 34342, Turkey.
Ender KaracaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Shalini N JhangianiHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Matthew N BainbridgeHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Kim S LawsonHuman Genetics Center and Institute of Molecular Medicine, University of Texas-Houston Health Science Center, Houston, TX 77030, USA.
Davut PehlivanDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Yuji OkamotoDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Marjorie WithersDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Pedro ManciasDivision of Child & Adolescent Neurology, Department of Neurology and Pediatrics, University of Texas Medical School at Houston, Houston, TX 77030, USA.
Anne SlavotinekDivision of Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA.
Pamela J ReitnauerPediatric Teaching Program, Cone Health System and UNC-Chapel Hill, Greensboro, NC 27401, USA.
Meryem T GoksungurDepartment of Neurology, Istanbul University, Istanbul Medical Faculty, Istanbul 34093, Turkey.
Michael ShyDepartment of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Thomas O CrawfordDepartments of Neurology and Pediatrics, Johns Hopkins University, Baltimore, MD 21218, USA.
Michel KoenigInstitut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), CNRS-INSERM-Universite de Strasbourg, Illkirch 67404, France; INSERM UMR_S 827, Institut Universitaire de Recherche Clinique and Laboratoire de Génétique Moléculaire, Centre Hospitalier Universitaire de Montpellier, Montpellier 34093, France.
Jason WillerCenter for Human Disease Modeling, Duke University, Durham, NC 27701, USA.
Brittany N FloresCellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Igor PediaditrakisCenter for Human Disease Modeling, Duke University, Durham, NC 27701, USA.
Onder UsDepartment of Neurology, Acibadem Kozyatagı Hospital, Istanbul 34742, Turkey.
Wojciech WiszniewskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Yesim ParmanDepartment of Neurology, Istanbul University, Istanbul Medical Faculty, Istanbul 34093, Turkey.
Anthony AntonellisCellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Neurology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Donna M MuznyHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Baylor-Hopkins Center for Mendelian Genomics
Nicholas KatsanisCenter for Human Disease Modeling, Duke University, Durham, NC 27701, USA.
Esra BattalogluDepartment of Molecular Biology and Genetics, Bogazici University, Istanbul 34342, Turkey.
Eric BoerwinkleHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Human Genetics Center and Institute of Molecular Medicine, University of Texas-Houston Health Science Center, Houston, TX 77030, USA.
Richard A GibbsDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
James R LupskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA. Electronic address: jlupski@bcm.edu.
Baylor College of Medicine · USDuke University · USUniversity of Michigan–Ann Arbor · USBoğaziçi University · TRIstanbul University · TRAcıbadem Adana Hospital · TRCone Health · USInserm · FRJohns Hopkins University · USThe University of Texas Health Science Center at Houston · USUniversity of California, San Francisco · USUniversity of Iowa · US
Funding
The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3MMICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3MProject 3P50MH094268 · NIMH · JOHNS HOPKINS UNIVERSITY · PI AVRAMOPOULOS, DIMITRIOS · 2011 to 2020
$19.9MtrainingU54NS065712 · NINDS · WAYNE STATE UNIVERSITY · PI SHY, MICHAEL E. · 2009 to 2023
$19.6MBaylor-Johns Hopkins Center for Mendelian GeneticsU54HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2012 to 2015
$15.6MCELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8MMEDICAL GENETICS RESEARCH FELLOWSHIP PROGRAMT32GM007526 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI Brendan Lee · 1985 to 2026
$11.4MNonrecurrent rearrangements, genome architecture and neurodegenerative disease.R01NS058529 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI LUPSKI, JAMES R. · 2009 to 2017
$5.0MGenomic Studies in Charcot-Marie-Tooth DiseaseR01NS075764 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SHY, MICHAEL E., ZUCHNER, STEPHAN · 2012 to 2016
$3.0MGenome analysis to elucidate molecular mechanisms for peripheral neuropathiesK23NS078056 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI WISZNIEWSKI, WOJCIECH KRZYSZTOF · 2012 to 2016
$783kThe role of glycyl-tRNA synthetase in axonal health and diseaseF30NS092238 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GRIFFIN, LAURIE BETH · 2015 to 2016
$40kNHGRI NIH HHS U54 HG003273NHGRI NIH HHS U54HG003273NHGRI NIH HHS U54 HG006542NHGRI NIH HHS U54HG006542NIGMS NIH HHS GM007315NIGMS NIH HHS GM07863NIGMS NIH HHS T32 GM007315NIGMS NIH HHS T32 GM007526NIGMS NIH HHS T32 GM007863NIGMS NIH HHS T32 GM07526-37NIMH NIH HHS P50 MH094268NINDS NIH HHS F30 NS092238NINDS NIH HHS K23 NS078056NINDS NIH HHS K23NS078056NINDS NIH HHS NS092238NINDS NIH HHS R01 NS058529NINDS NIH HHS R01NS058529NINDS NIH HHS R01 NS075764NINDS NIH HHS R01NS075764NINDS NIH HHS U54 NS065712NINDS NIH HHS U54NS065712
Abstract
Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES) of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ∼ 45% (17/37) of families. Three candidate disease genes are proposed, supported by a combination of genetic and in vivo studies. Aggregate analysis of mutation data revealed a significantly increased number of rare variants across 58 neuropathy-associated genes in subjects versus controls, confirmed in a second ethnically discrete neuropathy cohort, suggesting that mutation burden potentially contributes to phenotypic variability. Neuropathy genes shown to have highly penetrant Mendelizing variants (HPMVs) and implicated by burden in families were shown to interact genetically in a zebrafish assay exacerbating the phenotype established by the suppression of single genes. Our findings suggest that the combinatorial effect of rare variants contributes to disease burden and variable expressivity.
Indexed as
ExomeGenetic LoadPhenotypeAnimalsCharcot-Marie-Tooth DiseaseFemaleGenetic VariationHSP40 Heat-Shock ProteinsHumansMaleMutationMyelin P2 ProteinPedigreePenetrancePeripheral Nervous System DiseasesSerine C-PalmitoyltransferaseDNAJB5 protein, humanHSP40 Heat-Shock ProteinsMyelin P2 ProteinPMP2 protein, humanSerine C-PalmitoyltransferaseSPTLC3 protein, human
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.