RAD50 – Nijmegen breakage syndrome-like disorder

Limited evidence supports an autosomal recessive association between RAD50 and Nijmegen breakage syndrome-like disorder. A single unrelated proband was reported with a homozygous deep intronic RAD50 variant causing activation of a cryptic exon and reduced RAD50 expression, consistent with clinical features of the syndrome (PMID:39666384). No segregation information is available.

Functional work using a minigene splicing assay confirmed that the intronic change leads to aberrant distant exon activation and loss of normal transcript, providing mechanistic support but limited broader validation (PMID:39666384). Additional unrelated cases and in vivo models are needed to elevate the clinical validity of this gene–disease link.

References

• The Journal of clinical investigation • 2024 • A deep intronic mutation causes RAD50 deficiency through an unusual mechanism of distant exon activation PMID:39666384

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