Author:

Keywords:

Adult, Aged, DNA, Female, Fragile X Syndrome, Humans, Male, Mental Retardation, Mental Status Schedule, Middle Aged, Models, Genetic, Mutation, Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, FRAGILE-X-SYNDROME, CHROMOSOME INACTIVATION MOSAICISM, HETEROZYGOUS CARRIERS, CGG REPEAT, RETARDATION, FREQUENCY, INSTABILITY, EXPRESSION, PHENOTYPE, Intellectual Disability, 06 Biological Sciences, 11 Medical and Health Sciences, 31 Biological sciences, 32 Biomedical and clinical sciences, 42 Health sciences

Abstract:

The cloning of the FMR1 gene enables molecular diagnosis in patients and in carriers (male and female) of this X-linked mental retardation disorder. Unlike most X-linked disorders, a considerable proportion of the female carriers of a full mutation of the FMR1 gene is affected. In this study, the intelligence quotients (IQs) were ascertained by the Wechsler Adult Intelligence Scale in 33 adult females with a full mutation, with 28 first-degree adult female relatives (mainly sisters) without a full mutation as controls. Seventy-one percent of the females with a full mutation had IQ scores below 85. In paired analysis, no significant correlation could be detected between the IQs of the females with a full mutation and those of their first-degree female relatives, reflecting a dominant effect of the FMR1 gene full mutation in the mental development of females. Considering females with a full mutation only, we observed a significant relation between the proportion of normal FMR1 alleles on the active X chromosome and IQ. We present a model to explain this relationship.