A significant neurodevelopmental disorder associated with a South Asian founder mutation in the UFMylation adaptor CDK5RAP3 - Summary - MDSpire

A significant neurodevelopmental disorder associated with a South Asian founder mutation in the UFMylation adaptor CDK5RAP3

  • By

  • Michaela Yuen

  • Katharine Zhang

  • Rhett G. Marchant

  • Ryosuke Ishimura

  • Mark Graham

  • May Aung-Htut

  • Samantha Bryen

  • Rocio Rius

  • Lee Marshall

  • Nader Aryamanesh

  • Gregory Dziaduch

  • Himanshu Joshi

  • Ben Weisburd

  • Steve D. Wilton

  • Meredith Wilson

  • Russell Gear

  • Lucy Hennington

  • Stephanie Lau

  • Helen Doyle

  • Michael Krivanek

  • Richard J. Leventer

  • Susan M. White

  • Sarah A. Sandaradura

  • Masaaki Komatsu

  • Frances J. Evesson

  • Sandra T. Cooper

  • April 27, 2026

  • 0 min

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Objective:

To investigate the association of biallelic CDK5RAP3 variants with a severe neurodevelopmental disorder in individuals from two unrelated families, characterized by significant clinical manifestations.

Key Findings:
  • Biallelic variants in CDK5RAP3 were identified in three individuals from two unrelated families, suggesting a potential genetic basis for the disorder.
  • The identified variants are linked to a lethal neurodevelopmental disorder characterized by global developmental delay and other severe neurological symptoms, highlighting the need for clinical awareness.
  • CDK5RAP3 plays a critical role in UFMylation, impacting neurodevelopment, which may inform future therapeutic strategies.
Interpretation:

The findings suggest that CDK5RAP3 is essential for normal neurodevelopment, and its disruption leads to severe clinical manifestations.

Limitations:
  • The study is limited by the small number of families analyzed, which may restrict the generalizability of the findings.
  • Further research is needed to understand the full spectrum of CDK5RAP3-related disorders, including potential phenotypic variability.
Conclusion:

This study establishes a novel link between CDK5RAP3 mutations and severe neurodevelopmental disorders, highlighting the importance of UFMylation in human development and suggesting avenues for future research and clinical intervention.

Original Source(s)

A significant neurodevelopmental disorder associated with a South Asian founder mutation in the UFMylation adaptor CDK5RAP3

  • by Michaela Yuen, Katharine Zhang, Rhett G. Marchant, Ryosuke Ishimura, Mark Graham, May Aung-Htut, Samantha Bryen, Rocio Rius, Lee Marshall, Nader Aryamanesh, Gregory Dziaduch, Himanshu Joshi, Ben Weisburd, Steve D. Wilton, Meredith Wilson, Russell Gear, Lucy Hennington, Stephanie Lau, Helen Doyle, Michael Krivanek, Richard J. Leventer, Susan M. White, Sarah A. Sandaradura, Masaaki Komatsu, Frances J. Evesson, Sandra T. Cooper

  • April 27, 2026

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