BAZ2B – Neurodevelopmental Disorder

The bromodomain adjacent to zinc finger 2B gene (BAZ2B) encodes a chromatin remodeling protein. Haploinsufficiency of BAZ2B has been implicated in a Neurodevelopmental Disorder characterized by global developmental delay, intellectual disability, and autism spectrum disorder.

Exome-based analyses revealed an excess of de novo loss-of-function variants in BAZ2B in individuals with neurodevelopmental disorders. The study subsequently identified seven additional unrelated individuals with heterozygous deletions, stop-gain, or de novo missense variants presenting with developmental delay, intellectual disability, and/or ASD (PMID:31999386).

All variants were observed in a heterozygous de novo state, consistent with autosomal dominant inheritance, and no segregation beyond the probands has been reported.

The variant spectrum comprises predicted loss-of-function alleles such as c.3868C>T (p.Arg1290Ter), multiple canonical splice-site changes (c.3471+2dup, c.3075+1G>A, c.4213+1G>A, c.5797-1G>C, c.6210-3T>C), and a de novo missense change c.5599G>A (p.Asp1867Asn).

Functional bioinformatic analyses demonstrated a high degree of co-expression and convergence of BAZ2B with established neurodevelopmental and ASD genes during fetal cortical development, supporting a mechanism of haploinsufficiency.

These combined genetic and functional findings support a moderate clinical validity classification for BAZ2B in neurodevelopmental disorders. BAZ2B haploinsufficiency should be considered in the diagnostic workup of patients with developmental delay, intellectual disability, and features of ASD.

References

• Human Mutation • 2020 • BAZ2B haploinsufficiency as a cause of developmental delay, intellectual disability, and autism spectrum disorder. PMID:31999386

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