TRPS1 mutation detection in Chinese patients with Tricho-rhino-phalangeal syndrome and identification of four novel mutations.
TRPS1 mutation detection in Chinese patients with Tricho-rhino-phalangeal syndrome and identification of four novel mutations.
复制标题
中国毛鼻-指骨综合征患者TRPS1突变检测及4个新突变的鉴定
DOI：
10.1002/mgg3.1417
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发表时间：
2020-10
影响因子：
2
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Wang C;Xu Y;Qing Y;Yao R;Li N;Wang X;Yu T;Wang J
三鼻趾骨综合征（TRPS）是一种罕见的常染色体显性遗传疾病，其特征为颅面和骨骼畸形，包括身材矮小、稀疏的头皮毛发、稀疏的侧眉、梨形鼻和锥形骨骺。这种情况是由TRPS 1基因的单倍不足或显性负效应引起的。在这项研究中，我们分析了五个无关的TRPS患者的临床和遗传数据。根据临床和放射学特征（包括典型的头发和面部特征以及不同程度的骨骼异常），他们被怀疑患有TRPS。进行了下一代测序，以鉴定5名患者的TRPS 1基因变体。在患者1中，我们发现了c.1338C>A（p.Tyr446*）的新突变（de novo）。患者2具有脑积水和Arnold-Chiari综合征的新表型，我们还发现了c.2657C>A（p.Ser886*）处的母系遗传的新突变。患者3在c.2726G>C（p.Cys909Ser）处具有导致更严重表型的从头新突变。患者4在c.2762G>A（p.Arg921Gln）处具有父系遗传的已知突变。具有新型肝病表型的患者5在[GRCh 37] del（8）（q23.3-q24.11）chr 8：g.116，420，724 - 119，124，058（超过2，700 kb）处具有新型缺失。此外，在TRPS 1的加塔结合结构域中携带错义变体的患者3表现出更严重的颅面和骨骼表型。我们描述了四个新的突变和两个新的表型在5例患者。我们对TRPS突变的研究拓宽了TRPS的突变和表型谱。我们的研究结果揭示了TRPS 1的分子分析，以提高TRPS的临床诊断的意义。在这项研究中，我们描述了5例中国TRPS患者，包括每个患者的临床表现和分子特征。我们在5例患者中发现了4种新的突变和2种新的表型。我们相信我们的研究对文献做出了重大贡献，因为它增加了越来越多的研究，这些研究描述了TRPS 1基因突变引起的疾病的性质。
Tricho‐rhino‐phalangeal syndrome (TRPS) is a rare autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, a pear‐shaped nose, and cone‐shaped epiphyses. This condition is caused by haploinsufficiency or dominant‐negative effect of the TRPS1 gene. In this study, we analyzed the clinical and genetic data of five unrelated TRPS patients. They were suspected of having TRPS on the basis of clinical and radiological features including typical hair and facial features, as well as varying degrees of skeletal abnormalities. Next‐generation sequencing was performed to identify variants of the TRPS1 gene in the five patients. In patient 1, we found a novel mutation at c.1338C>A (p.Tyr446*) (de novo). Patient 2 had a novel phenotype of hydrocephaly and Arnold–Chiari syndrome and we also found a maternally inherited novel mutation at c.2657C>A (p.Ser886*). Patient 3 had a de novo novel mutation at c.2726G>C (p.Cys909Ser) leading to more severe phenotypes. Patient 4 had a paternally inherited known mutation at c.2762G>A (p.Arg921Gln). Patient 5 with a novel phenotype of hepatopathy had a novel deletion at [GRCh37] del(8)(q23.3‐q24.11) chr8:g.116,420,724‐119,124,058 (over 2,700 kb). In addition, the patient 3 who harboring missense variants in the GATA binding domain of TRPS1 showed more severe craniofacial and skeletal phenotypes. We describe four novel mutations and two novel phenotypes in five patients. The mutational and phenotypic spectrum of TRPS is broadened by our study on TRPS mutations. Our results reveal the significance of molecular analysis of TRPS1 for improving the clinical diagnosis of TRPS. In this study, we described five Chinese patients of TRPS, including the clinical presentation and molecular features of each patient. We found four novel mutations and two novel phenotypes in five patients. And we believe that our study makes a significant contribution to the literature because it adds to a growing body of studies that characterize the nature of conditions arising from mutations in the TRPS1 gene.
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影响因子：
1.3
作者：
Selenti N;Tzetis M;Braoudaki M;Gianikou K;Kitsiou-Tzeli S;Fryssira H
通讯作者：
Fryssira H
影响因子：
5.2
作者：
Kaiser, FJ;Brega, P;Lüdecke, HJ
通讯作者：
Lüdecke, HJ
影响因子：
3.5
作者：
Napierala, Dobrawa;Sam, Kathy;Lee, Brendan
通讯作者：
Lee, Brendan
影响因子：
2
作者：
Stagi, Stefano;Bindi, Giuseppe;Chiarelli, Francesco
通讯作者：
Chiarelli, Francesco
影响因子：
9.8
作者：
Lüdecke, HJ;Schaper, J;Horsthemke, B
通讯作者：
Horsthemke, B