Dysosteosclerosis is also caused by TNFRSF11A mutation

Guo, Long; Elçioğlu, Nursel; Karalar, Ozge K; Topkar, Osman Mert; Wang, Zheng; Sakamoto, Yuma; Matsumoto, Naomichi; Miyake, Noriko; Nishimura, Gen; Ikegawa, Shiro

doi:10.1038/s10038-018-0447-6

Cited by 21 publications

(33 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results suggest that the TNFRSF11A ‐associated dominant disorders characterized by enhanced bone resorption are induced by monoallelic gain‐of‐function mutations, whereas OP‐AR7 is caused by biallelic loss‐of‐function mutations. Recently, we reported the first splice‐site mutation of TNFRSF11A (c.616+3A>G) in DOS . The variant c.784G>T identified in this study seemed to be a nonsense mutation at first glance, but was actually a splicing mutation.…”

Section: Discussionsupporting

confidence: 66%

“…However, the serum osteoclast marker TRACP‐5b was within the normal range in this patient. Similarly, the serum osteoclast maker CTX (130 pg/mL; normal range, 25 to 573 pg/mL) was also normal in the first case reported previously by us . The inconsistent result between serum osteoclast makers and in vitro osteoclastogenesis assays suggests that the mutation effect on osteoclast differentiation is mild and tends to be compromised by in vivo factors to some extent.…”

Section: Discussionmentioning

confidence: 93%

“…One is the solute carrier family 29, member 3 ( SLC29A3 , MIM *612373), where homozygous and compound heterozygous missense mutations were identified in five unrelated individuals with DOS . We found the other gene in a Turkish patient, the tumor necrosis factor receptor superfamily member 11a ( TNFRSF11A , MIM *603499, AKA: receptor activator of nuclear factor‐kappa B, RANK ), where a homozygous splice‐site mutation caused skipping of an exon . Although many DOS cases have been reported, causal mutations have been identified only in these six patients and hence the total number of responsible genes for DOS and genotype‐phenotype correlation remain unclear.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

TNFRSF11A-Associated Dysosteosclerosis: A Report of the Second Case and Characterization of the Phenotypic Spectrum

Xue

Wang

Shinagawa

et al. 2019

Journal of Bone and Mineral Research

Self Cite

View full text Add to dashboard Cite

Dysosteosclerosis (DOS) is a distinct form of sclerosing bone disease characterized by irregular osteosclerosis and platyspondyly. DOS is genetically heterogeneous; however, only five cases with SLC29A3 mutations and a single case with a splice-site mutation of TNFRSF11A have been reported, and TNFRSF11A is also a causal gene for osteopetrosis, autosomal recessive 7 (OP-AR7). Thus, the causal genes of DOS and their genotype-phenotype associations remain unclear. In this study, we examined a Japanese patient with DOS and found a novel variant in TNFRSF11A. The homozygous variant was a G to T transversion at the first nucleotide of exon 9 (c.784G>T). Although the variant was predicted to cause a stop codon mutation (p.E262*), in silico evaluation of the exonic splicing elements followed by RT-PCR for the patient-derived cells showed that it caused aberrant splicing due to the change in the exonic splicing element and produced two types of aberrant transcripts: One caused a premature stop codon (p.E262Vfs*17) leading to nonsense mutation-mediated mRNA decay; the other produced a protein with interstitial deletion (p.E262_Q279del). The effects of the mutation on five splicing isoforms of TNFRSF11A were different from those in OP-AR7, but comparable with those in the first DOS with the TNFRSF11A mutation. Thus, we identified the second case of DOS caused by the TNFRSF11A splice-site mutation and confirmed the novel disease entity.

show abstract

Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

TNFRSF11A-Associated Dysosteosclerosis: A Report of the Second Case and Characterization of the Phenotypic Spectrum

Xue

Wang

Shinagawa

et al. 2019

Journal of Bone and Mineral Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…But studies also showed an opposite function in some other types of cancer [39]. The tumor necrosis factor receptor superfamily member 11a (TNFRSF11A) is the receptor for RANK ligand (RANKL) and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation and activation [40]. The vasoactive intestinal peptide receptor-1 (VIPR1) has an important neuropeptide that controls lung physiology and main functions.…”

mentioning

confidence: 99%

Identification of Prognostic Immune-Related Genes by Integrating mRNA Expression and Methylation in Lung Adenocarcinoma

Zhu

Wang

2020

International Journal of Genomics

View full text Add to dashboard Cite

Background. There is plenty of evidence showing that immune-related genes (IRGs) and epigenetic modifications play important roles in the biological process of cancer. The purpose of this study is to establish novel IRG prognostic markers by integrating mRNA expression and methylation in lung adenocarcinoma (LUAD). Methods and Results. The transcriptome profiling data and the RNA-seq data of LUAD with the corresponding clinical information of 543 LUAD cases were downloaded from The Cancer Genome Atlas (TCGA) database, which were analyzed by univariate Cox proportional regression and multivariate Cox proportional regression to develop an independent prognostic signature. On the basis of this signature, we could divide LUAD patients into the high-risk, medium-risk, and low-risk groups. Further survival analyses demonstrated that high-risk patients had significantly shorter overall survival (OS) than low-risk patients. The signature, which contains 8 IRGs (S100A16, FGF2, IGKV4-1, CX3CR1, INHA, ANGPTL4, TNFRSF11A, and VIPR1), was also validated by data from the Gene Expression Omnibus (GEO) database. We also conducted analyses of methylation levels of the relevant IRGs and their CpG sites. Meanwhile, their associations with prognosis were examined and validated by the GEO database, revealing that the methylation levels of INHA, S100A16, the CpG site cg23851011, and the CpG site cg06552037 may be used as the potential regulators for the treatment of LUAD. Conclusion. Collectively, INHA, S100A16, the CpG site cg23851011, and the CpG site cg06552037 are promising biomarkers for monitoring the outcomes of LUAD.

show abstract

“…A rare osteoclast-poor form of osteopetrosis, called dysosteosclerosis (DOS), accompanied by red violet macular atrophy, platyspondyly and metaphyseal osteosclerosis, is caused by mutations of the SLC29A3 (solute carrier family 29 member 3) gene encoding for a lysosomal nucleoside transporter highly expressed in myeloid cells (21, 55). More recently a novel splice-site mutation in the intron 6 of TNFRSF11A has been described in one patient indicating TNFRSF11A as additional gene responsible for DOS (56).…”

Section: Autosomal Recessive Osteopetrosis (Aro)mentioning

confidence: 99%

One Disease, Many Genes: Implications for the Treatment of Osteopetroses

et al. 2019

View full text Add to dashboard Cite

Osteopetrosis is a condition characterized by increased bone mass due to defects in osteoclast function or formation. In the last decades, the molecular dissection of osteopetrosis has unveiled a plethora of molecular players responsible for different forms of the disease, some of which present also primary neurodegeneration that severely limits the therapy. Hematopoietic stem cell transplantation can cure the majority of them when performed in the first months of life, highlighting the relevance of an early molecular diagnosis. However, clinical management of these patients is constrained by the severity of the disease and lack of a bone marrow niche that may delay immune reconstitution. Based on osteopetrosis genetic heterogeneity and disease severity, personalized therapies are required for patients that are not candidate to bone marrow transplantation. This review briefly describes the genetics of osteopetrosis, its clinical heterogeneity, current therapy and innovative approaches undergoing preclinical evaluation.

show abstract

Dysosteosclerosis is also caused by TNFRSF11A mutation

Cited by 21 publications

References 23 publications

TNFRSF11A-Associated Dysosteosclerosis: A Report of the Second Case and Characterization of the Phenotypic Spectrum

TNFRSF11A-Associated Dysosteosclerosis: A Report of the Second Case and Characterization of the Phenotypic Spectrum

Identification of Prognostic Immune-Related Genes by Integrating mRNA Expression and Methylation in Lung Adenocarcinoma

One Disease, Many Genes: Implications for the Treatment of Osteopetroses

Contact Info

Product

Resources

About