Fragile (X) X‐linked mental retardation I: Relationship between age and intelligence and the frequency of expression of fragil (X)(q28)

Abstract

Members of eight Saskatchewan families with fragile (X) X-linked mental retardation were studied in an attempt to relate frequency to age and intelligence. The mean IQ of 37 affected men was 35 (range 10-66). The mean IQ of 32 carriers was 88 (range 57-119), and the mean IQ of 13 females who remain at risk for being carriers, have no affected sons, and who failed to demonstrate the fra(X) was 100 (range 78-126). We demonstrated a significant inverse relationship between age and frequency of the fra(X) in carriers and in affected males. However, we demonstrated a more highly significant inverse relationship between frequency of the fra(X) and IQ in carriers but to a lesser extent in affected males. Of 32 carriers, only 3 (9.4%) did not demonstrate the fra(X) after addition of 5-fluoro-2'-deoxyuridine (FUdR) to the folic acid and thymidine-reduced culture medium. From these data we would recommend that chromosome studies in individuals at risk for fra(X) X-linked mental retardation be carried out at the youngest age and that the addition of FUdR to culture medium is useful in carrier identification. It is clear that, in at least the carriers, a lower expression of the fra(X) is highly significantly correlated to higher intelligence.

46,XY/47,XYY male with the fragile X syndrome: Cytogenetic and molecular studies

“…Mutation analvsis moved the + 1 . males and triple X females [Chudley, 1991;Fryns and van den Berghe, 1988;Chudley et al, 1983;Kahkonen, 1983;Fuster et al, 1988;Kupke et al, 19911, but not for 47,XYY males. Autosomal trisomies (mainly trisomy 21) have also been observed in association with the Fra(X) syndrome [Chudley, 1991;Chudley et al, 1988;Arinami et al, 19871 carrier sta& of his mother (and maternal aunt) in the face of negative Fra(X) cytogenetic results.…”

“…Whether or not there is a significant association between sex chromosomal or autosomal aneuploidy and the fragile X [Fra(X)] syndrome remains unclear [Chudley, 19911. However, multiple patients with Klinefelter syndrome and Fra(X) have been reported [Chudley, 1991;F'ryns and van den Berghe, 1988;Chudley et al, 1983;Wilmot et al, 19801. Triple-X mosaicism has been noted in association with cases of Fra(X) carriers [Kahkonen, 19831 and at least one patient with concurrent triple-X and F'ra(X) syndrome has been reported [Fuster et al, 19883.…”

Fragile X syndrome: Growth, development, and intellectual function

“…Longitudinal evaluation of intellectual function of a single case by Rhoads et a1 and of series of fra(X) males at varying ages have suggested that significant regression in mental abilities may occur as the patient gets older [Rhoads et al, 1982; Sutherland and Hecht, 1985;Chudley et al, 1983, Fryns and Van den Berghe, 1983; Mattei et al, 1981;Nielsen, 19831. While regression as measured by IQ test performance may be documented during the preadult and adult years, this is not a conspicuous manifestation.…”

Segregation analysis of rare autosomal folate sensitive fragile sites

“…Four porcent to 56Vo of metaphases express fragile X in affected males (Howard-Peebles, 1983). In one study, Chudley et al (1983) found the expression of fragile X in affected males varied between 5Vo and 50Vo (average -Z\Vo), soudek et al (1984) found that the proportion of positive cells was usually consistent in an individual over tims, and they hypothesised that the proporrion may be related to other familial or genetic factors rather than directly to the degree of retardation. Annerén et al, in which that breakage occurred."…”