Department of Neurology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200336, China.
WuXiDiagnostice, No. 31 Yiwei Road Waigaoqiao Pilot Free Trade Zone, Shanghai, 200131, China.
BMC Med Genomics. 2021 Oct 9;14(1):242. doi: 10.1186/s12920-021-01089-5.
Joubert syndrome (JS) is a group of rare congenital disorders characterized by cerebellar vermis dysplasia, developmental delay, and retina dysfunctions. Herein, we reported a Chinese patient carrying a new variant in the AHI1 gene with mild JS, and the 3D structure of the affected Jouberin protein was also predicted.
The patient was a 31-year-old male, who presented difficulty at finding toys at the age of 2 years, night blindness from age of 5 years, intention tremor and walking imbalance from 29 years of age. Tubular visual field and retina pigmentation were observed on ophthalmology examinations, as well as molar tooth sign on brain magnetic resonance imaging (MRI). Whole exome sequence revealed two compound heterozygous variants at c.2105C>T (p.T702M) and c.1330A>T (p.I444F) in AHI1 gene. The latter one was a novel mutation. The 3D protein structure was predicted using I-TASSER and PyMOL, showing structural changes from functional β-sheet and α-helix to non-functional D-loop, respectively.
Mild JS due to novel variants at T702M and I444F in the AHI1 gene was reported. The 3D-structural changes in Jouberin protein might underlie the pathogenesis of JS.
杰特综合征（JS）是一组罕见的先天性疾病，其特征为小脑蚓部发育不良、发育迟缓以及视网膜功能障碍。本文报道了一例携带 AHI1 基因新变异的中国患者，其表现为轻度 JS，并预测了受影响的杰贝林蛋白的 3D 结构。
患者为 31 岁男性，2 岁时出现寻找玩具困难，5 岁时出现夜盲，29 岁时出现意向性震颤和行走不稳。眼科检查发现管状视野和视网膜色素沉着，脑部磁共振成像（MRI）显示磨牙征。全外显子组测序显示 AHI1 基因中存在两个复合杂合变异，c.2105C>T（p.T702M）和 c.1330A>T（p.I444F）。后者为新突变。使用 I-TASSER 和 PyMOL 预测 3D 蛋白结构，分别显示从功能性β-折叠和α-螺旋到非功能性 D 环的结构变化。
报道了一例由 AHI1 基因中的 T702M 和 I444F 新变异引起的轻度 JS。杰贝林蛋白的 3D 结构变化可能是 JS 发病机制的基础。
