| First Author | Philibert RA | Year | 1998 |
| Journal | Mol Psychiatry | Volume | 3 |
| Issue | 4 | Pages | 303-9 |
| PubMed ID | 9702738 | Mgi Jnum | J:65306 |
| Mgi Id | MGI:1926276 | Doi | 10.1038/sj.mp.4000442 |
| Citation | Philibert RA, et al. (1998) Association of an X-chromosome dodecamer insertional variant allele with mental retardation [published erratum appears in Mol Psychiatry 1999 Mar;4(2):197]. Mol Psychiatry 3(4):303-9 |
| abstractText | Mental retardation is a prominent feature of many neurodevelopmental syndromes. In an attempt to identify genetic components of these illnesses, we isolated and sequenced a large number of human genomic cosmid inserts containing large trinucleotide repeats. One of these cosmids, Cos-4, maps to the X-chromosome and contains the sequence of a 7.3-kb mRNA. Initial polymorphism analysis across a region of repetitive DNA in this gene revealed a rare 12-bp exonic variation (<< 1% in non-iII males) having an increased prevalence in non-Fragile X males with mental retardation (4%, P < 0.04, n = 81). This variant was not present in the highly conserved mouse homologue that has 100% amino acid identity to the human sequence near the polymorphism. Subsequent screening of two additional independent cohorts of non-Fragile X mentally retarded patients and ethnically matched controls demonstrated an even higher prevalence of the 12-bp variant in males with mental retardation (8%, P < 0.0003, n = 125, and 14%, P < 0.10, n = 36) vs the controls. Multivariate analysis was conducted in an effort to identify other phenotypic components in affected individuals, and the findings suggested an increased incidence of histories of hypothyroidism (P < 0.001) and treatment with antidepressants (P < 0.001). We conclude that the presence of this 12-bp variant confers significant susceptibility for mental retardation. |
