Journal ArticleDOI
Dysosteosclerosis is also caused by TNFRSF11A mutation.
Long Guo,Nursel Elcioglu,Ozge K Karalar,Mert Osman Topkar,Zheng Wang,Yuma Sakamoto,Naomichi Matsumoto,Noriko Miyake,Gen Nishimura,Shiro Ikegawa +9 more
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TLDR
The study identified the second disease gene for DOS, TNFRSF11A, which may have the different roles in skeletal development and metabolism and the predicted effect of the mutation for the isoforms was different from those of the previously reported mutations, which could explain the difference of their phenotypes.Abstract:
Dysosteosclerosis (DOS) is a form of sclerosing bone disease characterized by irregular osteosclerosis and platyspondyly. Its mode of inheritance is autosomal recessive. SLC29A3 mutations have been reported as the causal gene in two DOS families, however, genetic heterogeneity has been suggested. By whole-exome sequencing in a Turkish patient with DOS, we found a novel splice-site mutation in TNFRSF11A. TNFRSF11A mutations have previously been reported in two autosomal dominant diseases (osteolysis, familial expansile and Paget disease of bone 2, early-onset) and an autosomal recessive disease (osteopetrosis, autosomal recessive 7). The biallelic mutation, c.616+3A>G, identified in our study was located in the splice donor site of intron 6 of TNFRSF11A. Exon trapping assay indicated the mutation caused skipping of exon 6, which was predicted to induce a frame-shift and an early termination codon in all known alternative transcript variants of TNFRSF11A. The predicted effect of the mutation for the isoforms was different from those of the previously reported mutations, which could explain the difference of their phenotypes. Thus, our study identified the second disease gene for DOS. TNFRSF11A isoforms may have the different roles in skeletal development and metabolism.read more
Citations
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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 L. Yamamoto,José Francisco da Silva Franco,Rachel Sayuri Honjo,Chong Ae Kim,Camila Manso Musso,Margaret Timmons,Amy Pizzino,Ryan J. Taft,Bryan R. Lajoie,Melanie A. Knight,Kenneth H. Fischbeck,Andrew B. Singleton,Carlos Ferreira,Zheng Wang,Li Yan,James Y. Garbern,Pelin Ozlem Simsek-Kiper,Hirofumi Ohashi,Pamela Gehron Robey,Alan Boyde,Naomichi Matsumoto,Noriko Miyake,J. Spranger,Raphael Schiffmann,Adeline Vanderver,Gen Nishimura,Maria Rita Passos-Bueno,Cas Simons,Cas Simons,Kinya Ishikawa,Shiro Ikegawa +38 more
TL;DR: The 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 CSF 1R function.
Journal ArticleDOI
One Disease, Many Genes: Implications for the Treatment of Osteopetroses.
Sara Penna,Sara Penna,Valentina Capo,Eleonora Palagano,Cristina Sobacchi,Anna Villa,Anna Villa +6 more
TL;DR: Based on osteopetrosis genetic heterogeneity and disease severity, personalized therapies are required for patients that are not candidate to bone marrow transplantation.
Journal ArticleDOI
Sclerosing bone dysplasias with hallmarks of dysosteosclerosis in four patients carrying mutations in SLC29A3 and TCIRG1.
Antonia Howaldt,Sheela Nampoothiri,Lisa-Marie Quell,Ayse Ozden,Björn Fischer-Zirnsak,Corinne Collet,Marie-Christine de Vernejoul,Hakan Doneray,Hülya Kayserili,Uwe Kornak,Uwe Kornak +10 more
TL;DR: The finding that intermediate autosomal recessive osteopetrosis due to TCIRG1 splice site mutations can also present with platyspondyly further increases the molecular heterogeneity of dysosteosclerosis-like sclerosing bone dysplasias.
Journal ArticleDOI
Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation
Antonia Howaldt,Anna Floriane Hennig,Anna Floriane Hennig,Tim Rolvien,Uta Rössler,Nina Stelzer,Alexej Knaus,Sebastian Böttger,Jozef Zustin,Sven Geißler,Ralf Oheim,Michael Amling,Hans-Peter Howaldt,Uwe Kornak +13 more
TL;DR: Analysis indicates a strong overlap of LRRK1‐related OSMD with other forms of intermediate osteopetrosis, but an exceptional abnormality of osteoclast resorption.
Journal ArticleDOI
Novel and recurrent COL11A1 and COL2A1 mutations in the Marshall–Stickler syndrome spectrum
Long Guo,Nursel Elcioglu,Zheng Wang,Yasemin Kendir Demirkol,Pinar Isguven,Naomichi Matsumoto,Gen Nishimura,Noriko Miyake,Shiro Ikegawa +8 more
TL;DR: This study examined four Turkish families with Marshall–Stickler syndrome using whole-exome sequencing and identified one COL2A1 mutation and three COL11A1 mutations, two of which were novel.
References
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Journal ArticleDOI
Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis.
Anne E. Hughes,Stuart H. Ralston,J. Marken,C. Bell,Heather MacPherson,R. G. H. Wallace,W. Van Hul,Michael P. Whyte,Kiyoshi Nakatsuka,L. Hovy,D. M. Anderson +10 more
TL;DR: Two heterozygous insertion mutations in exon 1 of TNFRSF11A in affected members of four families with FEO or familial Paget disease of bone caused an increase in RANK-mediated nuclear factor-κB signalling in vitro, consistent with the presence of an activating mutation.
Journal ArticleDOI
Nosology and classification of genetic skeletal disorders: 2015 revision
Luisa Bonafé,Valérie Cormier-Daire,Christine Hall,Ralph S. Lachman,Geert Mortier,Stefan Mundlos,Stefan Mundlos,Gen Nishimura,Luca Sangiorgi,Ravi Savarirayan,David Sillence,J. Spranger,Andrea Superti-Furga,Matthew L. Warman,Sheila Unger +14 more
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Bi-allelic CSF1R Mutations Cause Skeletal Dysplasia of Dysosteosclerosis-Pyle Disease Spectrum and Degenerative Encephalopathy with Brain Malformation.
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