Abstract:
BACKGROUND:Distal arthrogryposis (DA) is a group of clinically and genetically heterogeneous disorders that involve multiple congenital limb contractures and comprise at least 10 clinical subtypes. Here, we describe our findings in two Chinese families: Family 1 with DA2B (MIM 601680) and Family 2 with mild DA. METHODS:To map the disease locus, two-point linkage analysis was performed with microsatellite markers closed to TPM2, TNNI2/TNNT3 and TNNC2. In Family 1, a positive LOD (logarithm of odds) score was only obtained at the microsatellite marker close to TPM2 and mutation screening was performed using direct sequencing of TPM2 in the proband. In Family 2, for the LOD score that did not favor linkage to any markers, whole-exome sequencing (WES) was performed on the proband. PCR-restriction fragment length polymorphism (RFLP) and bioinformatics analysis were then applied to identify the pathogenic mutations in two families. In order to correlate genotype with phenotype in DA, retrospective analyses of phenotypic features according to the TPM2 and PIEZO2 mutation spectrums were carried out. RESULTS:A heterozygous missense mutation c.308A > G (p.Q103R) in TPM2 in Family 1, and a novel variation c.8153G > A (p.R2718Q) in PIEZO2 in Family 2 were identified. Each of the two novel variants was co-segregated with the DA manifestations in the corresponding family. Bioinformatics analysis from several tools supported the pathogenicity of the mutations. Furthermore, our study suggests that there is no relation between the types or locations of TPM2 mutations and the clinical characteristics, and that different inheritance modes and mutation types concerning PIEZO2 cause distinct clinical manifestations. CONCLUSIONS:We report two novel mutations within TPM2 and PIEZO2 responsible for DA2B and mild DA in two Chinese families, respectively. Our study expands the spectrum of causal mutations in the TPM2 and PIEZO2 genes.
journal_name
BMC Med Genetjournal_title
BMC medical geneticsauthors
Li S,You Y,Gao J,Mao B,Cao Y,Zhao X,Zhang Xdoi
10.1186/s12881-018-0692-8subject
Has Abstractpub_date
2018-10-03 00:00:00pages
179issue
1issn
1471-2350pii
10.1186/s12881-018-0692-8journal_volume
19pub_type
杂志文章abstract:BACKGROUND:I/D polymorphisms of ACE are associated with the plasma ACE concentration. The ACE is associated with the angiogenesis of ovarian endothelium in vitro as well as steroidogenesis and follicular growth in cattle. Since ACE induces a high blood supply and hypersteroidogenesis in the ovary, it may be associated ...
journal_title:BMC medical genetics
pub_type: 杂志文章
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abstract:BACKGROUND:The platelet P2Y12 receptor plays a key role in platelet activation. The H2 haplotype of the P2Y12 receptor gene (P2RY12) has been found to be associated with maximal aggregation response to adenosine diphosphate (ADP) and with increased risk for peripheral arterial disease. No data are available on its asso...
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更新日期:2020-02-17 00:00:00
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pub_type: 杂志文章,meta分析
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更新日期:2014-08-10 00:00:00
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更新日期:2012-07-20 00:00:00
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更新日期:2017-03-23 00:00:00
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doi:10.1186/1471-2350-14-1
更新日期:2013-01-08 00:00:00
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doi:10.1186/s12881-017-0445-0
更新日期:2017-08-03 00:00:00
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doi:10.1186/1471-2350-10-6
更新日期:2009-01-22 00:00:00
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更新日期:2001-01-01 00:00:00
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