Frontiers in Genetics (Jan 2024)

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

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

DOI
https://doi.org/10.3389/fgene.2023.1308116
Journal volume & issue
Vol. 14

Abstract

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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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