当前位置:
X-MOL 学术
›
Hum. Genet.
›
论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Recessive mutations in SCYL2 cause a novel syndromic form of arthrogryposis in humans.
Human Genetics ( IF 5.3 ) Pub Date : 2020-01-20 , DOI: 10.1007/s00439-020-02117-7 Mohammed Zain Seidahmed 1 , Adila Al-Kindi 2, 3 , Hessa S Alsaif 4 , Abeer Miqdad 1 , Nasser Alabbad 5 , Abdallah Alfifi 1 , Omer Bashir Abdelbasit 1 , Khalid Alhussein 1 , Abdulmohsen Alsamadi 1 , Niema Ibrahim 4 , Amna Al-Futaisi 6 , Almundher Al-Maawali 2, 3 , Fowzan S Alkuraya 4, 7
Human Genetics ( IF 5.3 ) Pub Date : 2020-01-20 , DOI: 10.1007/s00439-020-02117-7 Mohammed Zain Seidahmed 1 , Adila Al-Kindi 2, 3 , Hessa S Alsaif 4 , Abeer Miqdad 1 , Nasser Alabbad 5 , Abdallah Alfifi 1 , Omer Bashir Abdelbasit 1 , Khalid Alhussein 1 , Abdulmohsen Alsamadi 1 , Niema Ibrahim 4 , Amna Al-Futaisi 6 , Almundher Al-Maawali 2, 3 , Fowzan S Alkuraya 4, 7
Affiliation
Arthrogryposis multiplex congenita (AMC) is an important birth defect with a significant genetic contribution. Many syndromic forms of AMC have been described, but remain unsolved at the molecular level. In this report, we describe a novel syndromic form of AMC in two multiplex consanguineous families from Saudi Arabia and Oman. The phenotype is highly consistent, and comprises neurogenic arthrogryposis, microcephaly, brain malformation (absent corpus callosum), optic atrophy, limb fractures, profound global developmental delay, and early lethality. Whole-exome sequencing revealed a different homozygous truncating variant in SCYL2 in each of the two families. SCYL2 is a component of clathrin-coated vesicles, and deficiency of its mouse ortholog results in a severe neurological phenotype that largely recapitulates the phenotype observed in our patients. Our results suggest that severe neurogenic arthrogryposis with brain malformation is the human phenotypic consequence of SCYL2 loss of function mutations.
中文翻译:
SCYL2中的隐性突变在人类中引起新的关节炎形式的综合征形式。
多发性先天性关节炎(AMC)是重要的先天缺陷,具有重要的遗传贡献。已经描述了AMC的许多症状形式,但在分子水平上仍未解决。在此报告中,我们描述了来自沙特阿拉伯和阿曼的两个多重近亲家庭中AMC的新症状形式。该表型是高度一致的,并且包括神经性关节炎,小头畸形,脑畸形(无体),视神经萎缩,肢体骨折,严重的整体发育延迟和早期致死率。全外显子组测序揭示了两个家族中每个家族的SCYL2不同的纯合截短变体。SCYL2是网格蛋白包被的囊泡的成分,小鼠直系同源蛋白的缺乏及其缺陷会导致严重的神经表型,从而在很大程度上概括了我们患者中观察到的表型。我们的研究结果表明,严重的神经源性关节炎与脑畸形是SCYL2功能缺失的人类表型后果。
更新日期:2020-03-26
中文翻译:
SCYL2中的隐性突变在人类中引起新的关节炎形式的综合征形式。
多发性先天性关节炎(AMC)是重要的先天缺陷,具有重要的遗传贡献。已经描述了AMC的许多症状形式,但在分子水平上仍未解决。在此报告中,我们描述了来自沙特阿拉伯和阿曼的两个多重近亲家庭中AMC的新症状形式。该表型是高度一致的,并且包括神经性关节炎,小头畸形,脑畸形(无体),视神经萎缩,肢体骨折,严重的整体发育延迟和早期致死率。全外显子组测序揭示了两个家族中每个家族的SCYL2不同的纯合截短变体。SCYL2是网格蛋白包被的囊泡的成分,小鼠直系同源蛋白的缺乏及其缺陷会导致严重的神经表型,从而在很大程度上概括了我们患者中观察到的表型。我们的研究结果表明,严重的神经源性关节炎与脑畸形是SCYL2功能缺失的人类表型后果。