Loss-of-function variant in the LRR domain of SLITRK2 implicated in a neurodevelopmental disorder

被引:1
作者
Afsar, Tayyaba [1 ,2 ]
Fu, Hongxia [3 ]
Khan, Hammal [4 ]
Ali, Zain [5 ]
Zehri, Zamrud [6 ]
Zaman, Gohar [7 ]
Abbas, Safdar [8 ]
Mahmood, Arif [9 ,10 ]
Alam, Qamre [11 ]
Hu, Junjian [12 ]
Razak, Suhail [1 ,2 ]
Umair, Muhammad [2 ,13 ]
机构
[1] King Saud Univ, Coll Appl Med Sci, Dept Community Hlth Sci, Riyadh, Saudi Arabia
[2] King Salman Ctr Disabil Res, Riyadh, Saudi Arabia
[3] Dongguan Songshan Lake Cent Hosp, Dept Neurol, Dongguan, Peoples R China
[4] COMSATS Univ Islamabad, Dept Biosci, Islamabad, Pakistan
[5] Quaid I Azam Univ, Fac Biol Sci, Dept Biochem, Islamabad, Pakistan
[6] Civil Hosp, Dept Gynecol, Quetta, Pakistan
[7] Abbottabad Univ Sci & Technol, Dept Comp Sci, Abbottabad, Pakistan
[8] Dartmouth Coll, Dept Biol Sci, Hanover, NH USA
[9] Cent South Univ, Ctr Med Genet, Sch Life Sci, Changsha, Peoples R China
[10] Cent South Univ, Sch Life Sci, Hunan Key Lab Med Genet, Changsha, Peoples R China
[11] ExpressMed Diagnost & Res, Mol Genom & Precis Dept, Zinj, Bahrain
[12] Dongguan Songshan Lake Cent Hosp, Dept Cent Lab, Dongguan, Peoples R China
[13] King Saud Bin Abdulaziz Univ Hlth Sci, KAIMRC, Med Genom Res Dept, Minist Natl Guard Hlth Affairs MNGH, Riyadh, Saudi Arabia
关键词
neurodevelopmental disorders; SLITRK2; whole-exome sequencing; novel mutation; developmental anomaly; nonsense mutation; SEQUENCE VARIANTS; MUTATIONS;
D O I
10.3389/fgene.2023.1308116
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Neurodevelopmental disorders are characterized by different combinations of intellectual disability (ID), communication and social skills deficits, and delays in achieving motor or language milestones. SLITRK2 is a postsynaptic cell-adhesion molecule that promotes neurite outgrowth and excitatory synapse development. Methods and Results: In the present study, we investigated a single patient segregating Neurodevelopmental disorder. SLITRK2 associated significant neuropsychological issues inherited in a rare X-linked fashion have recently been reported. Whole-exome sequencing and data analysis revealed a novel nonsense variant [c.789T>A; p.(Cys263*); NM_032539.5; NP_115928.1] in exon 5 of the SLITRK2 gene (MIM# 300561). Three-dimensional protein modeling revealed substantial changes in the mutated SLITRK2 protein, which might lead to nonsense-medicated decay. Conclusion: This study confirms the role of SLITRK2 in neuronal development and highlights the importance of including the SLITRK2 gene in the screening of individuals presenting neurodevelopmental disorders.
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页数:9
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