ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation.
Investigation of a critical region for an X-linked mental retardation (XLMR) locus led us to identify a novel Aristaless related homeobox gene (ARX ). Inherited and de novo ARX mutations, including missense mutations and in frame duplications/insertions leading to expansions of polyalanine tracts in ARX, were found in nine familial and one sporadic case of MR. In contrast to other genes involved in XLMR, ARX expression is specific to the telencephalon and ventral thalamus. Notably there is an absence of expression in the cerebellum throughout development and also in adult. The absence of detectable brain malformations in patients suggests that ARX may have an essential role, in mature neurons, required for the development of cognitive abilities.
Bienvenu
Thierry
T
Institut Cochin - CHU Cochin Port-Royal, 75014 Paris, France.
Poirier
Karine
K
Friocourt
Gaelle
G
Bahi
Nadia
N
Beaumont
Delphine
D
Fauchereau
Fabien
F
Ben Jeema
Lamia
L
Zemni
Ramzi
R
Vinet
Marie-Claude
MC
Francis
Fiona
F
Couvert
Philippe
P
Gomot
Marie
M
Moraine
Claude
C
van Bokhoven
Hans
H
Kalscheuer
Vera
V
Frints
Suzanne
S
Gecz
Josef
J
Ohzaki
Kanae
K
Chaabouni
Habiba
H
Fryns
Jean-Pierre
JP
Desportes
Vincent
V
Beldjord
Cherif
C
Chelly
Jamel
J
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X; D015870:Gene Expression; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D010455:Peptides; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D025064:Sex Chromosome Disorders; D013687:Telencephalon / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
C469264:ARX protein, human; D018398:Homeodomain Proteins; D010455:Peptides; D014157:Transcription Factors; C019529:polyalanine