Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis.
Neural progenitor proliferation and migration influence brain size during neurogenesis. We report an autosomal recessive microcephaly syndrome cosegregating with a homozygous balanced translocation between chromosomes 3p and 10q, and we show that a position effect at the breakpoint on chromosome 3 silences the eomesodermin transcript (EOMES), also known as T-box-brain2 (TBR2). Together with the expression pattern of EOMES in the developing human brain, our data suggest that EOMES is involved in neuronal division and/or migration. Thus, mutations in genes encoding not only mitotic and apoptotic proteins but also transcription factors may be responsible for malformative microcephaly syndromes.
Baala
Lekbir
L
Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Maroc.
Briault
Sylvain
S
Etchevers
Heather C
HC
Laumonnier
Frédéric
F
Natiq
Abdelhafid
A
Amiel
Jeanne
J
Boddaert
Nathalie
N
Picard
Capucine
C
Sbiti
Aziza
A
Asermouh
Abdellah
A
Attié-Bitach
Tania
T
Encha-Razavi
Féréchté
F
Munnich
Arnold
A
Sefiani
Abdelaziz
A
Lyonnet
Stanislas
S
D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D061085:Agenesis of Corpus Callosum; D002879:Chromosomes, Human, Pair 10; D002893:Chromosomes, Human, Pair 3; D004252:DNA Mutational Analysis; D020868:Gene Silencing; D006720:Homozygote; D006801:Humans; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D010375:Pedigree; D020825:T-Box Domain Proteins / Q000235:genetics*; D014178:Translocation, Genetic
C491199:EOMES protein, human; D020825:T-Box Domain Proteins