Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis

Zhang, Shengquan; Jiang, Tao; Li, Min; Zhang, Xin; Ren, Yunqing; Wei, Shengcai; Sun, Liangdan; Cheng, Hui; Li, Yang; Yin, Xianyong; Hu, Zhengmao; Wang, Zhenying; Liu, Yuan; Guo, Baolei; Tang, Huayang; Tang, Xianfa; Ding, Yu; Wang, Jianbo; Ping, Li; Wu, Baoyu; Wang, Wen; Yuan, Xiangfeng; Hou, Jun-Sheng; Ha, Weiwei; Wang, Wenju; Zhai, Yujuan; Wang, Jing; Qian, Fu; Zhou, Fusheng; Chen, Gang; Zuo, Xianbo; Zheng, Xiaodong; Sheng, Yujun; Gao, Jinping; Liang, Bo; Li, Pan; Jun, Zhu; Xiao, Feng‐Li; Wang, Peiguang; Cui, Yong; Li, Hui; Liu, Shengxiu; Gao, Min; Fan, Xing; Shen, Songke; Zeng, Ming; Sun, Guangqing; Xu, Yu; Hu, Jing-Chu; He, Tingting; Li, Yingrui; Yang, Huanming; Wang, Jian; Zhong-yi, YU; Zhang, Huifeng; Hu, Xin; Yang, Ke; Wang, Jie; Zhao, Sihai; Zhou, Youwen; Liu, Jing; Du, Wei‐Dong; Zhang, Li; Xia, Kun; Yang, Sen; Wang, Jun; Zhang, Xuejun

doi:10.1038/ng.2409

Cited by 129 publications

(118 citation statements)

References 32 publications

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“…Exome sequencing becomes available and successfully used in disease gene mapping now with the rapid development of sequencing technology (Thompson et al 2012;Varela et al 2011;Wu et al 2012;Zhang et al 2012). With the expectation that exome sequencing markedly enhances the power of causal gene screening, we conducted an integrative analysis of exome sequencing and a genome-wide association study (GWAS) of grade II and III KBD.…”

Section: Introductionmentioning

confidence: 99%

Exome sequencing identified FGF12 as a novel candidate gene for Kashin-Beck disease

Zhang

Dai

Lin³

et al. 2015

Funct Integr Genomics

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The objective of this study was to identify novel causal genes involved in the pathogenesis of Kashin-Beck disease (KBD). A representative grade III KBD sib pair with serious skeletal growth and development failure was subjected to exome sequencing using the Illumina Hiseq2000 platform. The detected gene mutations were then filtered against the data of 1000 Genome Project, dbSNP database, and BGI inhouse database, and replicated by a genome-wide association study (GWAS) of KBD. Ninety grade II or III KBD patients with extreme KBD phenotypes and 1627 healthy controls were enrolled in the GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 was applied for genotyping. PLINK software was used for association analysis. We identified a novel 106T>C at the 3'UTR of the FGF12 gene, which has not been reported by now. Sequence alignment observed high conversation at the mutated 3'UTR+106T>C locus across various vertebrates. In the GWAS of KBD, we detected nine SNPs of the FGF12 gene showing association evidence (P value < 0.05) with KBD. The most significant association signal was observed at rs1847340 (P value = 1.90 × 10(-5)). This study suggests that FGF12 was a susceptibility gene of KBD. Our results provide novel clues for revealing the pathogenesis of KBD and the biological function of FGF12.

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Section: Introductionmentioning

confidence: 99%

Exome sequencing identified FGF12 as a novel candidate gene for Kashin-Beck disease

Zhang

Dai

Lin³

et al. 2015

Funct Integr Genomics

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“…5 As reported, overexpression of the MVK protein promoted the differentiation of keratinocyte differentiation marker keratin 1 and involucrin proteins, 2 and the expression of MVK could protect keratinocytes from UV-Ainduced apoptosis. 2 We performed functional prediction of the novel missense mutation (c.1106C>G) with the use of SIFT (Sorting Intolerant From Tolerant) (http://sift.bii.a-star.edu.sg/, Maintained by the group of Pauline Ng at Genome Institute of Singapore, Singapore, Singapore) and PolyPhen-2 (Polymorphism Phenotyping v2) (http://genetics.bwh.harvard.edu, Developed by Harvard Medical School, Boston, Massachusetts, USA) software ( Table 1). Both of the prediction results confirmed that the effect of the novel mutation was deleterious.…”

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confidence: 97%

A novel MVK gene mutation in a Chinese patient with disseminated superficial actinic porokeratosis

Yang

et al. 2015

Dermatologica Sinica

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“…This disorder results in hyperkeratosis, and patients present with non-contagious dry itchy lesions that typically worsen with sun exposure. Thus, mevalonic acid may playa role in protecting keratinocytes from apoptosis induced by ultraviolet radiations (21).…”

Section: Pieces Of the Clinical Puzzlementioning

confidence: 99%

Current Advances in the Understanding and Treatment of Mevalonate Kinase Deficiency

Esposito

Ascolese

Senatore

et al. 2014

Int J Immunopathol Pharmacol

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Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory metabolic disease that is caused by mutations in the MVK gene. Patients with MKD typically have an early onset in infancy. MKD is characterized by recurrent episodes of high fever, abdominal distress, diffuse joint pain, and skin rashes. In a subset of patients, MKD is also associated with elevated serum immunoglobulin D (IgD) levels (hyperimmunoglobulinemia D syndrome, HIDS). The clinical phenotype of MKD varies widely and depends on the severity of the impaired mevalonate kinase activity. Complete impairment results in the severe metabolic disease, mevalonic aciduria, while a partial deficiency results in a broad spectrum of clinical presentation, including HIDS. The precise molecular mechanisms behind the elevated serum IgD levels and inflammation that occurs in MKD remain unknown. Children who exhibit symptoms of MKD should be tested for mutations in the MKD gene. However, the complexity of MKD often results in delays in its definitive diagnosis and the outcome in adult age is not completely known. Therapeutic options for MKD are based on limited data and include non-steroidal anti-inflammatory drugs, corticosteroids, and biological agents that target specific cytokine pathways. Inrecent years, some studies have reported promising results for new biological drugs; however, these cas-eli ha'Ye failed to achieve satisfactory remission. Therefore, further studies are needed to understand the pathogenesis of MKD and identify innovative therapeutic tools for its management..

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Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis

Cited by 129 publications

References 32 publications

Exome sequencing identified FGF12 as a novel candidate gene for Kashin-Beck disease

Exome sequencing identified FGF12 as a novel candidate gene for Kashin-Beck disease

A novel MVK gene mutation in a Chinese patient with disseminated superficial actinic porokeratosis

Current Advances in the Understanding and Treatment of Mevalonate Kinase Deficiency

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