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Background <p>The <i>TRIP12</i> gene, encoding an E3 ligase involved in the ubiquitin-proteasome pathway, is implicated in Clark-Baraitser syndrome which causes neurodevelopmental delay and intellectual disability (ID). This study aims to present and characterize two distinct novel <i>TRIP12</i> variants in two unrelated Lebanese children with neurodevelopmental delay.</p> Methods <p>Exome sequencing (ES) was performed, followed by in silico assessment of variant impact on protein structure. Clinical and molecular findings were described. Literature review was carried out on previously published <i>TRIP12</i> variants.</p> Results <p>Patients demonstrated hypotonia, speech and motor delay. ES uncovered a paternally inherited missense variant in the <i>TRIP12</i> gene (c.5905T &gt; A nucleotide substitution) in patient 1, and a <i>de novo</i> indel variant causing an in-frame change (c.4532_4538delinsC) in patient 2. Affected amino acids in both variants were highly conserved, and structural analyses of mutant variants suggested altered TRIP12 protein structure. No phenotypic distinction emerged in comparison to 70 published <i>TRIP12</i> variants.</p> Conclusion <p>This study introduces the first Lebanese <i>TRIP12</i> variants in developmentally delayed patients. It expands the genotypic spectrum of <i>TRIP12</i>-related neurodevelopmental disorders and underscores their variable expressivity.</p>

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Novel TRIP12 variants in two Lebanese patients with neurodevelopmental delay

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月18日

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  • Simone Khalifeh,
  • Nadine J. Makhoul,
  • Samah Trad,
  • Sara Amro,
  • Medhat Siddik,
  • Joe Bedran,
  • Rose-Mary Boustany

摘要

Background

The TRIP12 gene, encoding an E3 ligase involved in the ubiquitin-proteasome pathway, is implicated in Clark-Baraitser syndrome which causes neurodevelopmental delay and intellectual disability (ID). This study aims to present and characterize two distinct novel TRIP12 variants in two unrelated Lebanese children with neurodevelopmental delay.

Methods

Exome sequencing (ES) was performed, followed by in silico assessment of variant impact on protein structure. Clinical and molecular findings were described. Literature review was carried out on previously published TRIP12 variants.

Results

Patients demonstrated hypotonia, speech and motor delay. ES uncovered a paternally inherited missense variant in the TRIP12 gene (c.5905T > A nucleotide substitution) in patient 1, and a de novo indel variant causing an in-frame change (c.4532_4538delinsC) in patient 2. Affected amino acids in both variants were highly conserved, and structural analyses of mutant variants suggested altered TRIP12 protein structure. No phenotypic distinction emerged in comparison to 70 published TRIP12 variants.

Conclusion

This study introduces the first Lebanese TRIP12 variants in developmentally delayed patients. It expands the genotypic spectrum of TRIP12-related neurodevelopmental disorders and underscores their variable expressivity.