Identification of a Novel Missense FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly Using Exome Sequencing

Deng, Hao; Lü, Qian; Xu, Hongbo; Deng, Xiong; Yuan, Lamei; Yang, Zhijian; Guo, Yi; Lin, Qiongfen; Xiao, Jingjing; Guan, Liping; Song, Zhi

doi:10.1371/journal.pone.0155908

Cited by 11 publications

(11 citation statements)

References 33 publications

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“…A prioritization scheme similar to those described in recent studies was used to identify proband pathogenic variants . Only a homozygous missense variant, c.1627G>A (p.V543M), in the GNE gene (NM_001128227, hGNE2 isoform NP_001121699) was suspected as the proband pathogenic variant.…”

Section: Resultsmentioning

confidence: 99%

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Identification of a GNE homozygous mutation in a Han‐Chinese family with GNE myopathy

Yuan

Guo

et al. 2018

J Cellular Molecular Medi

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GNE myopathy is a rare, recessively inherited, early adult‐onset myopathy, characterized by distal and proximal muscle degeneration which often spares the quadriceps. It is caused by mutations in the UDP‐N‐acetylglucosamine 2‐epimerase/N‐acetylmannosamine kinase gene (GNE). This study aimed to identify the disease‐causing mutation in a three‐generation Han‐Chinese family with members who have been diagnosed with myopathy. A homozygous missense mutation, c.1627G>A (p.V543M) in the GNE gene co‐segregates with the myopathy present in this family. A GNE myopathy diagnosis is evidenced by characteristic clinical manifestations, rimmed vacuoles in muscle biopsies and the presence of biallelic GNE mutations. This finding broadens the GNE gene mutation spectrum and extends the GNE myopathy phenotype spectrum.

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Section: Resultsmentioning

confidence: 99%

“…A prioritization scheme similar to those described in recent studies was used to identify proband pathogenic variants. 13,18,19…”

Section: Gne Mutation Screeningmentioning

confidence: 99%

Identification of a GNE homozygous mutation in a Han‐Chinese family with GNE myopathy

Yuan

Guo

et al. 2018

J Cellular Molecular Medi

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“…It is noteworthy that meta-analysis in the Thai population discovered novel SLE susceptible variants on FBN2. The FBN2 allele is located on a chromosome 5 encoded protein called fibrillin-2 [62]. Fibrillins-2 is one of the glycoprotein components incorporated extracellularly on microfibrils and is essential in bone, muscle, and extracellular matrix formation [63].…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of genome-wide association study identifies FBN2 as a novel locus associated with systemic lupus erythematosus in Thai population

et al. 2020

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Background: Differences in the expression of variants across ethnic groups in the systemic lupus erythematosus (SLE) patients have been well documented. However, the genetic architecture in the Thai population has not been thoroughly examined. In this study, we carried out genome-wide association study (GWAS) in the Thai population. Methods: Two GWAS cohorts were independently collected and genotyped: discovery dataset (487 SLE cases and 1606 healthy controls) and replication dataset (405 SLE cases and 1590 unrelated disease controls). Data were imputed to the density of the 1000 Genomes Project Phase 3. Association studies were performed based on different genetic models, and pathway enrichment analysis was further examined. In addition, the performance of disease risk estimation for individuals in Thai GWAS was assessed based on the polygenic risk score (PRS) model trained by other Asian populations. Results: Previous findings on SLE susceptible alleles were well replicated in the two GWAS. The SNPs on HLA class II (rs9270970, A>G, OR = 1.82, p value = 3.61E−26), STAT4 (rs7582694, C>G, OR = 1.57, p value = 8.21E−16), GTF2I (rs73366469, A>G, OR = 1.73, p value = 2.42E−11), and FAM167A-BLK allele (rs13277113, A>G, OR = 0.68, p value = 1.58E−09) were significantly associated with SLE in Thai population. Meta-analysis of the two GWAS identified a novel locus at the FBN2 that was specifically associated with SLE in the Thai population (rs74989671, A>G, OR = 1.54, p value = 1.61E−08). Functional analysis showed that rs74989671 resided in a peak of H3K36me3 derived from CD14+ monocytes and H3K4me1 from T lymphocytes. In addition, we showed that the PRS model trained from the Chinese population could be applied in individuals of Thai ancestry, with the area under the receiver-operator curve

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“…It is noteworthy that meta-analysis in the Thai population discovered novel SLE susceptible variants on FBN2. The FBN2 allele is located on a chromosome 5 encoded protein called brillin-2 [60]. Fibrillins-2 is one of the glycoprotein components incorporated extracellularly on micro brils and is essential in bone, muscle, and extracellular matrix formation [61].…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of genome-wide association study identifies FBN2 as a novel locus associated with Systemic Lupus Erythematosus in Thai population

Tangtanatakul

Thumarat

Satproedprai³

et al. 2020

Preprint

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Background: Differences in the expression of variants across ethnic groups in the Systemic Lupus Erythematosus (SLE) patients have been well documented. However, the genetic architecture in the Thai population has not been thoroughly examined. In this study, we carried out genome-wide association study (GWAS) in the Thai population. Methods: Two GWAS cohorts were independently collected and genotyped: discovery dataset (487 SLE cases and 1,606 healthy controls) and replication dataset (405 SLE cases and 1,590 unrelated-disease controls). Data were imputed to the density of the 1,000 Genomes Project Phase 3. Association studies were performed based on different genetic models, and pathway enrichment analysis was further examined. In addition, the performance of disease risk estimation for individuals in Thai GWAS was assessed based on the polygenic risk score (PRS) model trained by other Asian populations. Results: Previous findings on SLE susceptible alleles were well replicated in the two GWAS. The SNPs on HLA-class II (rs9270970, A>G, OR=1.82, p-value = 3.61E-26), STAT4 (rs7582694, C>G, OR=1.57, p-value = 8.21E-16), GTF2I (rs73366469, A>G, OR=1.73, p-value = 2.42E-11) and FAM167A-BLK allele (rs13277113, A>G, OR=0.68, p-value = 1.58E-09) were significantly associated with SLE in Thai population. Meta-analysis of the two GWAS identified a novel locus at the FBN2 that was specifically associated with SLE in the Thai population (rs74989671, A>G, OR=1.54, p-value = 1.61E-08). Functional analysis showed that rs74989671 resided in a peak of H3K36me3 derived from CD14+ monocytes and H3K4me1 from T-lymphocytes. In addition, we showed that the PRS model trained from the Chinese population could be applied in individuals of Thai ancestry, with the area under the receiver-operator curve (AUC) achieving 0.76 for this predictor. Conclusions: We demonstrated the genetic architecture of SLE in the Thai population and identified a novel locus associated with SLE. Also, our study suggested a potential use of the PRS model from the Chinese population to estimate the disease risk for individuals of Thai ancestry.

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Identification of a Novel Missense FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly Using Exome Sequencing

Cited by 11 publications

References 33 publications

Identification of a GNE homozygous mutation in a Han‐Chinese family with GNE myopathy

Identification of a GNE homozygous mutation in a Han‐Chinese family with GNE myopathy

Meta-analysis of genome-wide association study identifies FBN2 as a novel locus associated with systemic lupus erythematosus in Thai population

Meta-analysis of genome-wide association study identifies FBN2 as a novel locus associated with Systemic Lupus Erythematosus in Thai population

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