A Novel Missense Mutation in Peripheral Myelin Protein-22 Causes Charcot-Marie-Tooth Disease

Li, Lixi; Dong, Hai‐Lin; Xiao, Bao‐Guo; Wu, Zhi‐Ying

doi:10.4103/0366-6999.211539

Cited by 10 publications

(9 citation statements)

References 27 publications

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“…One hundred and fifty unrelated CMT patients consisting of 96 males and 54 females were recruited from Second Affiliated Hospital of Zhejiang University School of Medicine and Huashan Hospital of Fudan University between December 2007 and August 2018. Patients were evaluated and diagnosed by at least two senior neurologists according to the strategy described in our previous reports . This study was approved by the local Ethics Committees for medical research.…”

Section: Methodsmentioning

confidence: 99%

“…7,8 Owing to CMT's clinical and genetic heterogeneity, it is expensive and time-consuming to screen all the possible causative genes using conventional Sanger sequencing. However, highthroughput targeted next-generation sequencing (NGS) has been employed successfully in CMT 9,10 and other neurogenetic diseases such as amyotrophic lateral sclerosis (ALS), [11][12][13] hereditary spastic paraplegia (HSP), 14,15 and hereditary ataxia (HA). 16,17 Consequently, nearly 90 genes associated with CMT and other inherited peripheral neuropathies have been assembled in a gene panel, and parallel sequencing can be performed to interrogate these genes.…”

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confidence: 99%

“…Patients were evaluated and diagnosed by at least two senior neurologists according to the strategy described in our previous reports. 9,10 This study was approved by the local Ethics Committees for medical research. Written informed consents were obtained from participants or their guardians.…”

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confidence: 99%

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Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot‐Marie‐Tooth disease

et al. 2019

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Charcot‐Marie‐Tooth (CMT) disease is a heterogeneous group of inherited sensorimotor neuropathies. To clarify the genetic spectrum and clinical profiles in Chinese CMT patients, we enrolled 150 unrelated CMT patients from southeast China. We performed multiplex ligation‐dependent probe amplification (MLPA) testing in all patients and next‐generation sequencing (NGS) among those patients without PMP22 rearrangements. We identified PMP22 duplications in 40 patients and deletions in 12 patients. In addition, we found 19 novel variants and 36 known mutations in 57 patients. Among these 55 variants, 45 pathogenic or likely pathogenic variants were identified in 48 cases, and 10 variants with uncertain significance were identified in 9 cases. Therefore, we obtained a genetic diagnosis in 63.8% (88/138) of CMT patients and 66.7% (100/150) of all included patients. PMP22, GJB1, and MFN2 are the most common causative genes in CMT1 (demyelinated form), intermediate CMT, and CMT2 (axonal form), respectively. In this study, we identified a higher proportion of intermediate CMT, a relatively high frequency of NDRG1 mutations and clinical features of later onset age in CMT1A patients. Our results broaden the genetic and clinical spectrum of CMT patients, which can help optimize the genetic and clinical diagnosis.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot‐Marie‐Tooth disease

et al. 2019

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“…Researching the relation between sequence and structure in protein has the great scienti c interest [18], and we can use the sequences to explore the protein evolution and function [19,20]. Studies reported that the missense mutations caused by the sequence variations were related to the protein function to account for the phenotype variations [21][22][23][24]. Here, we identi ed a missense mutation (g.17303383G > T), and it changed the protein secondary structure by prediction with the SOPMA.…”

Section: Discussionmentioning

confidence: 98%

Determination of genetic effects and functional SNPs of bovine HTR1B gene on milk fatty acid traits

Cao

Shi

Peng

et al. 2020

Preprint

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Background: Our previous genome-wide association study (GWAS) on milk fatty acid traits in Chinese Holstein cows revealed, the SNP, BTB-01556197, was significantly associated with C10:0 at genome-wide level (P = 0.0239). It was located in the down-stream of 5-hydroxytryptamine receptor 1B (HTR1B) gene that has been shown to play an important role in the regulation of fatty acid oxidation. Hence, we considered it as a promising candidate gene for milk fatty acids in dairy cattle. In this study, we aimed to investigate whether the HTR1B gene had significant genetic effects on milk fatty acid traits.Results: We re-sequenced the entire coding region and 3,000 bp of 5' and 3' flanking regions of HTR1B gene. A total of 13 SNPs was identified, containing one in 5' flanking region, two in 5' untranslated region (UTR), two in exon 1, five in 3' UTR, and three in 3' flanking region. By performing genotype-phenotype association analysis with SAS9.2 software, we observed that 13 SNPs were significantly associated with medium-chain saturated fatty acids such as C6:0, C8:0 and C10:0 (P < 0.0001 ~ 0.042). With Haploview 4.1 software, linkage disequilibrium (LD) analysis was performed that two haplotype blocks formed by two and ten SNPs were observed. Haplotype-based association analysis indicated that both haplotype blocks were strongly associated with C6:0, C8:0 and C10:0 as well (P < 0.0001 ~ 0.0071). With regards to the missense mutation in exon 1 (g.17303383G>T) that reduced amino acid change from alanine to serine, we predicted that it altered the secondary structure of HTR1B protein with SOPMA. In addition, we predicted that three SNPs in promoter region, g.17307103A>T, g.17305206T>G and g.17303761C>T, altered the binding sites of transcription factors (TFs) HMX2, PAX2, FOXP1ES, MIZ1, CUX2, DREAM, and PPAR-RXR by Genomatix. Of them, luciferase assay experiment further confirmed that the allele T of g.17307103A>T significantly increased the transcriptional activity of HTR1B gene than allele A (P = 0.0007).Conclusions: In conclusion, our findings provided first evidence that the HTR1B gene had significant genetic effects on milk fatty acids in dairy cattle.

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“…[ 5 6 7 ] The clinical features of PMP2 -associated neuropathy were similar to PMP22 duplication. [ 6 8 ] BSCL2 pathogenic variants were originally identified in patients with AR congenital generalized lipodystrophy type 2 and were subsequently found to cause a broad spectrum of neurological disorders. [ 9 ] The BSCL2 pathogenic variant p.S90W was identified to cause AD-CMT2 in a Korean family, who presented predominant thenar muscle atrophy, frequent sensory disturbances, and pyramidal tract signs.…”

Section: Introductionmentioning

confidence: 99%

Screening for SH3TC2, PMP2, and BSCL2 Variants in a Cohort of Chinese Patients with Charcot-Marie-Tooth

Jiang

Yan

Liu

et al. 2018

Chinese Medical Journal

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Background:SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive (AR) Charcot-Marie-Tooth (CMT) disease type 1, autosomal dominant (AD)-CMT1, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families.Methods:A total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84 AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMT1 probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using polymerase chain reaction and Sanger sequencing. All these patients were out of 315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of pathogenic variants of PMP22, MFN2, MPZ, GJB1, GDAP1, HSPB1, HSPB8, EGR2, NEFL, and RAB7. Candidate variants were analyzed based on the standards and guidelines of American College of Medical Genetics and Genomics (ACMG). Clinical features were reevaluated.Results:We identified three novel heterozygous variants such as p.L95V (c.283C>G), p.L1048P (c.3143T>C), and p.V1105M (c.3313G>A) of SH3TC2 gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in silico and screening in the healthy control revealed that the three SH3TC2 variants were likely pathogenic, no second allele variants were discovered. According to the standards and guidelines of ACMG, the heterozygous SH3TC2 variants such as p.L95V, p.L1048P, and p.V1105M were considered to be of uncertain significance.Conclusions:SH3TC2, PMP2, and BSCL2 pathogenic variants might be rare in Chinese CMT patients. Further studies to confirm our findings are needed.

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A Novel Missense Mutation in Peripheral Myelin Protein-22 Causes Charcot-Marie-Tooth Disease

Cited by 10 publications

References 27 publications

Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot‐Marie‐Tooth disease

Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot‐Marie‐Tooth disease

Determination of genetic effects and functional SNPs of bovine HTR1B gene on milk fatty acid traits

Screening for SH3TC2, PMP2, and BSCL2 Variants in a Cohort of Chinese Patients with Charcot-Marie-Tooth

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