Section 5: BAF in Developmental Disorders (Chromatin

What are chromatinopathies?

Rare (often de novo) developmental disorders caused by mutations in genes encoding chromatin regulators like histone modifiers, remodelers, and other chromatin-associated proteins.

Give two examples of a chromatinopathy and the gene responsible.

Coffin-Siris syndrome (ARID1B) and Nicolaides-Baraitser syndrome (SMARCA2).

What is Coffin-Siris syndrome characterized by?

Intellectual disability, coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails.

What type of mutation in ARID1B is a frequent cause of Coffin-Siris syndrome?

Haploinsufficiency (de novo nonsense, frameshift mutations, or deletions).

What type of mutations in SMARCA2 cause Nicolaides-Baraitser syndrome?

Heterozygous de novo missense mutations.

Besides BAF complex genes, what other chromatin remodeler complex has been implicated in CSS-like phenotypes?

The NuRD complex, through mutations in PHF6.

Why are there so many different chromatinopathies with varied symptoms?

Because chromatin regulators have specific functions in controlling cell fate decisions during development, and their disruption can affect many different tissues and pathwa