Evidence map›Paper›PMID 30982609›Full record

ArticleAmerican journal of human genetics2019

Bi-allelic CSF1R Mutations Cause Skeletal Dysplasia of Dysosteosclerosis-Pyle Disease Spectrum and Degenerative Encephalopathy with Brain Malformation.

Long Guo, Débora Romeo Bertola, Asako Takanohashi, Asuka Saito, Yuko Segawa, Takanori Yokota, Satoru Ishibashi, Yoichiro Nishida, Guilherme Lopes Yamamoto, José Francisco da Silva Franco and 28 more

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In one paragraph

Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

79 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.

  1. Pooled it
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  8. Macrophages in embryonic development.Nature reviews. Immunology · 2026
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19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors at 20 institutions in 8 countries.

Long GuoLaboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo 108-8639, Japan.
Débora Romeo BertolaUnidade de Genética Clínica, Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil; Instituto de Biociências da Universidade de São Paulo, São Paulo 05508-090, Brazil. Electronic address: debora.bertola@usp.br.
Asako TakanohashiDivision of Neurology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
Asuka SaitoDepartment of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Yuko SegawaDepartment of Orthopedic Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Takanori YokotaDepartment of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Satoru IshibashiDepartment of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Yoichiro NishidaDepartment of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Guilherme Lopes YamamotoUnidade de Genética Clínica, Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil; Instituto de Biociências da Universidade de São Paulo, São Paulo 05508-090, Brazil.
José Francisco da Silva FrancoUnidade de Genética Clínica, Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
Rachel Sayuri HonjoUnidade de Genética Clínica, Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
Chong Ae KimUnidade de Genética Clínica, Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
Camila Manso MussoInstituto de Biociências da Universidade de São Paulo, São Paulo 05508-090, Brazil.
Margaret TimmonsDevelopmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
Amy PizzinoDivision of Neurology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ryan J TaftIllumina, Inc., 5200 Illumina Way, San Diego, CA 92122, USA.
Bryan LajoieIllumina, Inc., 5200 Illumina Way, San Diego, CA 92122, USA.
Melanie A KnightNeurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
Kenneth H FischbeckNeurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
Andrew B SingletonLaboratory of Neurogenetics, National Institute of Aging, NIH, Bethesda, MD 20892, USA.
Carlos R FerreiraMedical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA, and Division of Genetics and Metabolism, Children's National Health System, Washington, DC 20010, USA.
Zheng WangLaboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo 108-8639, Japan; Department of Medical Genetics, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, People's Republic of China.
Li YanDepartment of Neurology, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.
James Y GarbernCenter of Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
Pelin O Simsek-KiperDepartment of Pediatrics, Hacettepe University Medical Faculty, Ankara 06100, Turkey.
Hirofumi OhashiDivision of Medical Genetics, Saitama Children's Medical Center, Saitama 330-8777, Japan.
Pamela G RobeySkeletal Biology Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA.
Alan BoydeBiophysics, Oral Growth and Development, Dental Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Naomichi MatsumotoDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Noriko MiyakeDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Jürgen SprangerCentral German Competence Center for Rare Diseases (MKSE), Magdeburg 39120, Germany; Greenwood Genetic Center, Greenwood, SC 29646, USA.
Raphael SchiffmannBaylor Scott & White Research Institute, Dallas, TX 75204, USA.
Adeline VanderverDivision of Neurology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gen NishimuraIntractable Disease Center, Saitama University Hospital, Moro 350-0495, Japan.
Maria Rita Dos Santos Passos-BuenoInstituto de Biociências da Universidade de São Paulo, São Paulo 05508-090, Brazil.
Cas SimonsTranslational Bioinformatics Group, Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC 3052, Australia; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Kinya IshikawaDepartment of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Shiro IkegawaLaboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo 108-8639, Japan. Electronic address: sikegawa@ims.u-tokyo.ac.jp.
Tokyo Medical and Dental University · JPHospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo · BRNational Institute of Neurological Disorders and Stroke · USUniversidade de São Paulo · BRIllumina (United States) · USPhiladelphia University · USRIKEN Center for Integrative Medical Sciences · JPYokohama City University · JPBaylor Scott & White Health · USChina-Japan Friendship Hospital · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNHacettepe University · TRNational Human Genome Research Institute · USNational Institute of Dental and Craniofacial Research · USNational Institute on Aging · USQueen Mary University of London · GBSaitama Children's Medical Center · JPSaitama Medical University Hospital · JPSupply Chain Competence Center (Germany) · DEUniversity of Pennsylvania · US

Funding

The role of stem cells in skeletal health and diseaseZIADE000380 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI ROBEY, PAMELA G · 2009 to 2025
$30.6M
Genetic analysis in families with neurological diseaseZIAAG000958 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW · 2009 to 2024
$10.9M
Studies Of Hereditary Neurological Disease: Disease Gene IdentificationZIANS002974 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI FISCHBECK, KENNETH · 2009 to 2023
$9.8M
6 · The paper itself

Abstract

Colony stimulating factor 1 receptor (CSF1R) plays key roles in regulating development and function of the monocyte/macrophage lineage, including microglia and osteoclasts. Mono-allelic mutations of CSF1R are known to cause hereditary diffuse leukoencephalopathy with spheroids (HDLS), an adult-onset progressive neurodegenerative disorder. Here, we report seven affected individuals from three unrelated families who had bi-allelic CSF1R mutations. In addition to early-onset HDLS-like neurological disorders, they had brain malformations and skeletal dysplasia compatible to dysosteosclerosis (DOS) or Pyle disease. We identified five CSF1R mutations that were homozygous or compound heterozygous in these affected individuals. Two of them were deep intronic mutations resulting in abnormal inclusion of intron sequences in the mRNA. Compared with Csf1r-null mice, the skeletal and neural phenotypes of the affected individuals appeared milder and variable, suggesting that at least one of the mutations in each affected individual is hypomorphic. Our results characterized a unique human skeletal phenotype caused by CSF1R deficiency and implied that bi-allelic CSF1R mutations cause a spectrum of neurological and skeletal disorders, probably depending on the residual CSF1R function.

Indexed as

MutationAdolescentAdultAllelesAnimalsBrainChild, PreschoolFemaleHumansLeukoencephalopathiesMaleMiceMice, KnockoutOsteochondrodysplasiasOsteosclerosisPhenotypeCSF1R protein, humanCsf1r protein, mouseReceptor, Macrophage Colony-Stimulating FactorReceptors, Granulocyte-Macrophage Colony-Stimulating FactorCSF1RdysosteosclerosisHDLSleukoencephalopathymutationosteoclastosteosclerosisPyle diseaseskeletal dysplasia

Identifiers

PMID30982609
PMCPMC6507048
OpenAlexW2937350838

What OpenQuestion holds

Textmetadata
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.