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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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Guo, Long [1] ; Bertola, Debora Romeo [2, 3] ; Takanohashi, Asako [4] ; Saito, Asuka [5] ; Segawa, Yuko [6] ; Yokota, Takanori [5] ; Ishibashi, Satoru [5] ; Nishida, Yoichiro [5] ; Yamamoto, Guilherme Lopes [2, 3] ; da Silva Franco, Jose Francisco [3] ; Honjo, Rachel Sayuri [3] ; Kim, Chong Ae [3] ; Musso, Camila Manso [2] ; Timmons, Margaret [7] ; Pizzino, Amy [4] ; Taft, Ryan J. [8] ; Lajoie, Bryan [8] ; Knight, Melanie A. [9] ; Fischbeck, Kenneth H. [9] ; Singleton, Andrew B. [10] ; Ferreira, Carlos R. [11, 12] ; Wang, Zheng [1, 13, 14] ; Yan, Li [15] ; Garbern, James Y. [16] ; Simsek-Kiper, Pelin O. [17] ; Ohashi, Hirofumi [18] ; Robey, Pamela G. [19] ; Boyde, Alan [20] ; Matsumoto, Naomichi [21] ; Miyake, Noriko [21] ; Spranger, Juergen [22, 23] ; Schiffmann, Raphael [24] ; Vanderver, Adeline [4] ; Nishimura, Gen [25] ; dos Santos Passos-Bueno, Maria Rita [2] ; Simons, Cas [26, 27] ; Ishikawa, Kinya [5] ; Ikegawa, Shiro [1]
Total Authors: 38
Affiliation:
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[1] RIKEN Ctr Integrat Med Sci, Lab Bone & Joint Dis, Tokyo 1088639 - Japan
[2] Univ Sao Paulo, Inst Biociencias, BR-05508090 Sao Paulo - Brazil
[3] Univ Sao Paulo, Unidade Genet Clin, Inst Crianca, Hosp Clin, Fac Med, BR-05403000 Sao Paulo - Brazil
[4] Univ Penn, Div Neurol, Childrens Hosp Philadelphia, Philadelphia, PA 19104 - USA
[5] Tokyo Med & Dent Univ, Dept Neurol & Neurol Sci, Grad Sch, Tokyo 1138519 - Japan
[6] Tokyo Med & Dent Univ, Dept Orthoped Surg, Grad Sch, Tokyo 1138519 - Japan
[7] NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 - USA
[8] Illumina Inc, 5200 Illumina Way, San Diego, CA 92122 - USA
[9] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 - USA
[10] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 - USA
[11] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 - USA
[12] Childrens Natl Hlth Syst, Div Genet & Metab, Washington, DC 20010 - USA
[13] Peking Union Med Coll, Dept Med Genet, Inst Basic Med Sci, Beijing 100005 - Peoples R China
[14] Chinese Acad Med Sci, Beijing 100005 - Peoples R China
[15] China Japan Friendship Hosp, Dept Neurol, Beijing 100029 - Peoples R China
[16] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 - USA
[17] Hacettepe Univ, Med Fac, Dept Pediat, TR-06100 Ankara - Turkey
[18] Saitama Childrens Med Ctr, Div Med Genet, Saitama 3308777 - Japan
[19] Natl Inst Dent & Craniofacial Res, Skeletal Biol Sect, NIH, Bethesda, MD 20892 - USA
[20] Queen Mary Univ London, Biophys Oral Growth & Dev, Dent Inst, Barts & London Sch Med & Dent, London E1 2AT - England
[21] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa 2360004 - Japan
[22] Greenwood Genet Ctr, Greenwood, SC 29646 - USA
[23] Cent German Competence Ctr Rare Dis MKSE, D-39120 Magdeburg - Germany
[24] Baylor Scott & White Res Inst, Dallas, TX 75204 - USA
[25] Saitama Univ Hosp, Intractable Dis Ctr, Moroyama 3500495 - Japan
[26] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072 - Australia
[27] Royal Childrens Hosp, Murdoch Childrens Res Inst, Translat Bioinformat Grp, Melbourne, Vic 3052 - Australia
Total Affiliations: 27
Document type: Journal article
Source: American Journal of Human Genetics; v. 104, n. 5, p. 925-935, MAY 2 2019.
Web of Science Citations: 7
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. (AU)

FAPESP's process: 15/21783-9 - Analysis of genetic variants in rare osteochondrodysplasias using whole exome sequencing
Grantee:Débora Romeo Bertola
Support Opportunities: Regular Research Grants
FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC