Duplications of FOXG1 in 14q12 are associated with developmental epilepsy, mental retardation, and severe speech impairment.
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.
Brunetti-Pierri
Nicola
N
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. brunetti@tigem.it
Paciorkowski
Alex R
AR
Ciccone
Roberto
R
Della Mina
Erika
E
Bonaglia
Maria Clara
MC
Borgatti
Renato
R
Schaaf
Christian P
CP
Sutton
V Reid
VR
Xia
Zhilian
Z
Jelluma
Naftha
N
Ruivenkamp
Claudia
C
Bertrand
Mary
M
de Ravel
Thomy J L
TJ
Jayakar
Parul
P
Belli
Serena
S
Rocchetti
Katia
K
Pantaleoni
Chiara
C
D'Arrigo
Stefano
S
Hughes
Jeff
J
Cheung
Sau Wai
SW
Zuffardi
Orsetta
O
Stankiewicz
Pawel
P
D000328:Adult; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D007805:Language Development Disorders / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins