Duplications of FOXG1 in 14q12 are associated with developmental epilepsy, mental retardation, and severe speech impairment

Nicola Brunetti-Pierri, Alex R. Paciorkowski, Roberto Ciccone, Erika Della Mina, Maria Clara Bonaglia, Renato Borgatti, Christian P. Schaaf, V. Reid Sutton, Zhilian Xia, Naftha Jelluma, Claudia Ruivenkamp, Mary Bertrand, Thomy J.L. De Ravel, Parul Jayakar, Serena Belli, Katia Rocchetti, Chiara Pantaleoni, Stefano D'Arrigo, Jeff Hughes, Sau Wai CheungOrsetta Zuffardi, Pawel Stankiewicz

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


Genome-wide high-resolution array analysis is rapidly becoming a reliable method of diagnostic investigation in individuals with mental retardation and congenital anomalies, leading to the identification of several novel microdeletion and microduplication syndromes. We have identified seven individuals with duplication on chromosome 14q11.2q13.1, who exhibited idiopathic developmental delay and cognitive impairment, severe speech delay, and developmental epilepsy. Among these cases, the minimal common duplicated region on chromosome 14q11.2q13.1 includes only three genes, FOXG1, C14orf23, and PRKD1. We propose that increased dosage of Forkhead Box G1 (FOXG1) is the best candidate to explain the abnormal neurodevelopmental phenotypes observed in our patients. Deletions and inactivating mutations of FOXG1 have been associated with a Rett-like syndrome characterized by hypotonia, irritability, developmental delay, hand stereotypies, and deceleration of head growth. FOXG1, encoding a brain-specific transcription factor, has an important role in the developing brain. In fact, in vivo studies in chicken brain demonstrated that overexpression of FOXG1 results in thickening of the neuroepithelium and outgrowth of the telencephalon and mesencephalum, secondary to a reduction in neuroepithelial cell apoptosis.

Original languageEnglish
Pages (from-to)102-107
Number of pages6
JournalEuropean Journal of Human Genetics
Issue number1
StatePublished - Jan 2011


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