Heterozygous Expression of X-Linked Mental Retardation and X-Chromosome Marker Fra(X)(Q27)

Abstract

Males affected by one form of X-linked retardation possess the X-chromosomal marker fra(X)(q27) and are physically normal except for macro-orchidism. To relate possession of the marker X to phenotypic expression in female heterozygotes, we investigated 128 mildly retarded (IQ, 55 to 75) school-girls in Sydney, New South Wales, Australia. Seventy-two girls had no physical abnormalities and of these, five (7 per cent) carried the marker X. Investigation of relatives revealed retarded males in four of the five families. Pedigree and chromosomal analysis identified a further 18 heterozygotes; six were regarded as intellectually or educationally retarded. We conclude that expression of the X-linked mutation in female carriers contributes to mild mental retardation of girls, that those who are physically normal should be screened for the marker X, and that their relatives should be investigated in order to identify additional females with a high risk of conceiving affected males.

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

“…This is in keeping with the report by Turner et al [1980b], and we would presume that this is the result of random X-chromosome inactivation. We cannot eliminate a selection bias when studying our carriers since the dull carriers would be more easily accessible to us than the brighter ones who would tend to leave their families to seek better opportunities.…”

“…Thus, several biochemical aspects of fra(X) MR remain unsettled. Several investigators have noted that many obligate fra(X) MR carriers do not demonstrate the fra(X) and that it was an impression that the fra(X) expression is lower with increasing age and higher intelligence [Jacobs et al, 1980;Turner et al, 1980a;Turner et al, 1980b;Schmidt and Passarge, 19801. This creates uncertainty when faced with an older intelligent woman at risk of being a carrier.…”

Cognitive profiles of boys with the fragile X syndrome

“…Approximately one-third of heterozygotes have below average intelligence (IQ t 8 5 ) [Turner et al, 1980;Sherman et al, 1984;Fryns, 19861. When present, intellectual deficits are likely to range from learning disabilities to mild retardation [Kemper et al, 19861.…”

Fragile X expression in short‐term whole blood cultures is affected by cell density

“…It has been estimated that the fra(X) syndrome accounts for one-third to one-half of the families with X-linked MR [Turner et al, 1980;Carpenter et al, 19821. Incidence estimates of fra(X) in general populations range from 0.3 to 0.92/1000 [Herbst and Miller, 1980;Blomquist et al, 1982;Froster-Iskenius et al, 19831.…”

“…There are also reports of both obligate female and male carriers whose cultures do not exhibit fra(X) [Wolff et al, 1978;Sutherland, 1979b;Jacobs et al, 1980;Turner et al, 1980;Brandurn-Nielson et al, 1981;Webb et al, 1981Webb et al, , 1982Fryns and Van den Berghe, 1982;Popovich et al, 1982;Rhoads et al, 1982;Camerino et al, 1983;Gardner et al, 1983;Van Roy et al, 1983;Howard-Peebles and Friedman, 19851 and who appear to be physically and mentally normal. Such individuals are referred to as nonpenetrant carriers.…”