Investigating the Relationship Between FMR1 Allele Length and Cognitive Ability in Children: A Subtle Effect of the Normal Allele Range on the Normal Ability Range?

Abstract

SummaryThe FMR1 gene contains a trinucleotide repeat tract which can expand from a normal size of around 30 repeats to over 200 repeats, causing mental retardation (Fragile X Syndrome). Evidence suggests that premutation males (55-200 repeats) are susceptible to a late-onset tremor/ataxia syndrome and females to premature ovarian failure, and that intermediate alleles (∼ 41-55 repeats) and premutations may be in excess in samples with special educational needs. We explored the relationship between FMR1 allele length and cognitive ability in 621 low ability and control children assessed at 4 and 7 years, as well as 122 students with high IQ. The low and high ability and control samples showed no between-group differences in incidence of longer alleles. In males there was a significant negative correlation between allele length and non-verbal ability at 4 years (p = 0.048), academic achievement in maths (p = 0.003) and English (p = 0.011) at 7 years, and IQ in the high ability group (p = 0.018). There was a significant negative correlation between allele length and a standardised score for IQ and general cognitive ability at age 7 in the entire male sample (p = 0.002). This suggests that, within the normal spectrum of allele length, increased repeat numbers may have a limiting influence on cognitive performance.

Mineral trioxide aggregate solution inhibits osteoclast differentiation through the maintenance of osteoprotegerin expression in osteoblasts

“…A similar argument applies to the data in Aziz et al 2003, where the main manifestations in 6 PM and 4 GZ carriers aged 4–15 years comprised ASD, hyperactivity, and minor cognitive impairments. The only statistical evidence so far for the influence of small CGG repeat expansions on cognitive status was based on the finding of a significant link between the GZ alleles and reduced cognitive abilities in a large sample of male students aged 4–7 years [Loat et al, 2006]. In our data, we did not find significant correlations between neuropsychological and molecular measures, but considering small sample size the power of the test may have been inadequate.…”

Linking the FMR1 alleles with small CGG expansions with neurodevelopmental disorders: Preliminary data suggest an involvement of epigenetic mechanisms

“…A similar argument applies to the data in: Aziz et al [2003], where the main manifestations in 6 PM and 4 GZ carriers aged 4-15 years comprised ASD, hyperactivity, and minor cognitive impairments. The only statistical evidence so far for the influence of small CGG repeat expansions on cognitive status was based on the finding of a significant link between the GZ alleles and reduced cognitive abilities in a large sample of male students aged 4-7 years [Loat et al, 2006]. In our data, we did not find significant correlations between neuropsychological and molecular measures, but considering small sample size the power of the test may have been inadequate.…”

Motor deficits on a ladder rung task in male and female adolescent and adult CGG knock-in mice

“…Alternately, if animals showed a trend toward a general clumsiness or lack of precision in motor performance that could indicate a more purely motor deficit [4, 5]. The first possibility is intriguing in for the CGG KI mice as frontal-parietal network dysfunction is hypothesized to underlie spatiotemporal, arithmetic, and attentional deficits in FXS as well as the fragile X premutation [3, 10, 18–20, 28, 30, 32, 35, 39, 40, 43, 47, 51, 55, 60, 61], as well as being involved in skilled walking behaviors [2, 4, 5, 23, 45]. The latter possibility, based more directly on motor function is also important for the extension of the CGG KI mouse as a murine model of motor deficits present in FXTAS [62].…”