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

来源：

FRONTIERS IN GENETICS | 2024年 / 14卷

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.

引用

页数：9

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