The p.Arg377Trp variant in ACTL6A underlines a recognizable BAF-opathy phenotype

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• Reports a second patient with a de novo p.Arg377Trp variant in the ACTL6A gene.
• Phenotype includes dysmorphic facies and acral malformations, characteristic of BRG1-associated factor (BAF) complex disorders.
• Previous reports identified three patients with ACTL6A variants and neurodevelopmental delay.

Discussion:

• The p.Arg377Trp mutation in ACTL6A appears to cause a distinct BAFopathy phenotype.
• This specific phenotype is not observed in individuals with other ACTL6A mutations.
• Highlights the potential for genotype-specific manifestations within ACTL6A-related disorders.

Key Insights:

• Identifies a novel genotype-phenotype correlation for the ACTL6A gene.
• The p.Arg377Trp variant is associated with a recognizable BAFopathy syndrome.
• Adds to the understanding of genetic contributions to BAFopathies.

Outlook:

• Further research is needed to confirm and delineate the genotype-phenotype spectrum of ACTL6A variants.
• This finding may aid in the diagnosis and management of patients with similar phenotypes.
• Contributes to the broader understanding of chromatin remodeling complex disorders.