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) schoolgirls 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. (N Engl J Med. 1980; 303:662–4.)