AUTHOR=Afsar Tayyaba , Fu Hongxia , Khan Hammal , Ali Zain , Zehri Zamrud , Zaman Gohar , Abbas Safdar , Mahmood Arif , Alam Qamre , Hu Junjian , Razak Suhail , Umair Muhammad 

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

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1308116

DOI=10.3389/fgene.2023.1308116

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods and Results:</bold> 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&gt;A; p.(Cys263*); NM_032539.5; NP_115928.1] in exon 5 of the <italic>SLITRK2</italic> gene (MIM# 300561). Three-dimensional protein modeling revealed substantial changes in the mutated SLITRK2 protein, which might lead to nonsense-medicated decay.</p><p><bold>Conclusion:</bold> This study confirms the role of SLITRK2 in neuronal development and highlights the importance of including the <italic>SLITRK2</italic> gene in the screening of individuals presenting neurodevelopmental disorders.</p>