OPHN1 was first determined to be one of the genes associated with X-linked mental retardation; however, neither the gene's function nor the link between its expression and survival of patients has been investigated.
OPHN1 is involved in X-linked mental retardation (XLMR) with cerebellar hypoplasia and encodes a Rho-GTPase-activating protein called oligophrenin-1, which is produced throughout the developing mouse brain and in the hippocampus and Purkinje cells of the cerebellum in adult mice.
Polyglutamine tract binding protein-1, a causative gene for X-linked mental retardation, is also involved in RNA metabolism, and both mutation and duplication of the gene were reported in human patients.
ATRX is a member of the Snf2 family of chromatin-remodelling proteins and is mutated in an X-linked mental retardation syndrome associated with alpha-thalassaemia (ATR-X syndrome).
Mutation of the ATRX gene leads to X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome and several other X-linked mental retardation syndromes.
We also analyzed ACSL4 and DLG3, which have previously been known to cause XLMR and IL1RAPL2, a homologous gene for IL1RAPL1 that is mutated in autism and XLMR.
This study should help to identify the novel XLMR genes and mechanisms leading to MR and reveal the clinical conditions and genomic background of XLMR.
Detailed comparison of the clinical characteristics and the function of the genes located in the commonly duplicated regions of these patients led us to the hypothesis that an increased dosage of ATRX and perhaps of other genes is involved in the pathogenetic mechanism of this XLMR phenotype, including mental retardation, short stature, and genital abnormalities comprising cryptorchidism and/or a small penis.
Detailed comparison of the clinical characteristics and the function of the genes located in the commonly duplicated regions of these patients led us to the hypothesis that an increased dosage of ATRX and perhaps of other genes is involved in the pathogenetic mechanism of this XLMR phenotype, including mental retardation, short stature, and genital abnormalities comprising cryptorchidism and/or a small penis.