Recessive Loss of DIAPH1 Function Causes a Progressive Neurodevelopmental Syndrome with Variable Immunological Involvement - PubMed
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- #DIAPH1
- #Immunodeficiency
- #Neurodevelopmental disorder
- Biallelic DIAPH1 pathogenic variants cause a neurodevelopmental syndrome with variable immunodeficiency.
- Clinical features include developmental delay, intellectual disability, progressive microcephaly, cortical visual impairment or blindness, epilepsy, and frequent brain abnormalities.
- Almost half of the patients suffered from infections, mainly respiratory, related to epilepsy and aspiration.
- T-cell receptor excision circles and naïve T-lymphocyte counts were consistently low despite normal lymphocyte subsets and serum immunoglobulins.
- Vertebrate models (Xenopus and zebrafish) mirrored human growth and eye defects, with zebrafish showing seizure-like behavior.
- DIAPH1 is critical for neurodevelopment, immune regulation, and DNA repair, with potential implications for infection susceptibility, lymphoma, or treatment-related toxicity.
- Patients may be identified by TREC newborn screening before neurological symptoms develop due to impaired T-cell maturation.