TEAD1 – Aicardi Syndrome

Aicardi syndrome is a congenital neurodevelopmental disorder characterized by infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae. A de novo truncating variant in the autosomal gene TEAD1 (c.618G>A (p.Trp206Ter)) was identified in one female patient with AIC features, supporting a pathogenic role for TEAD1 in non-X-linked cases (PMID:26091538). RNA sequencing of patient blood revealed altered expression of genes involved in synaptic plasticity, neuronal and retinal development, and cell cycle control/apoptosis, suggesting a haploinsufficiency mechanism. The skewed X inactivation observed in this case further implicates TEAD1 dosage sensitivity in AIC pathogenesis. In a follow-up cohort of 38 well-characterized AIC patients, no additional TEAD1 or OCEL1 deleterious variants were detected (PMID:28361097), indicating the rarity of TEAD1-associated AIC. Thus, current evidence supports a limited clinical validity for TEAD1 in Aicardi syndrome, requiring further case confirmation and functional studies. Key take-home: TEAD1 truncating mutations should be considered in sporadic AIC with atypical inheritance, but routine screening is not yet justified.

References

• Investigative ophthalmology & visual science • 2015 • A De Novo Mutation in TEAD1 Causes Non-X-Linked Aicardi Syndrome. PMID:26091538
• Molecular genetics & genomic medicine • 2017 • Independent variant analysis of TEAD1 and OCEL1 in 38 Aicardi syndrome patients. PMID:28361097

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