BOD1 – Intellectual Disability

In a consanguineous Lebanese family with autosomal recessive Intellectual Disability, whole exome sequencing identified a homozygous nonsense variant c.451C>T (p.Arg151Ter) in BOD1, confirming involvement in cognitive impairment and syndromic features including neurodevelopmental delay and high-frequency hearing impairment (PMID:32578875). The same study reported a second independent homozygous stop-gain variant in an Iranian family, bringing the total to 2 probands with loss-of-function alleles (PMID:32578875).

BOD1 encodes a regulator of chromosome biorientation essential for accurate cell division and contributes to cell survival and fatty acid metabolism. Loss-of-function mutations likely act via autosomal recessive deficiency, though direct functional validation in patient-derived cells is pending. Additional case series and mechanistic studies are needed to confirm pathogenic pathways and support clinical screening.

Key Take-home: Homozygous BOD1 loss-of-function variants underlie a rare autosomal recessive intellectual disability syndrome with neurodevelopmental delay and hearing impairment, warranting inclusion in diagnostic gene panels for syndromic cognitive disorders.

References

• Clinical Genetics • 2020 • A homozygous stop gain mutation in BOD1 gene in a Lebanese patient with syndromic intellectual disability. PMID:32578875

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