Fragile X syndrome in an extended family with special reference to an affected male with Klinefelter syndrome.

We report on a large family (4 generations), with 77 studied individuals, 9 mentally retarded males, and one affected female with fragile X syndrome [fra(X)]. The analysis of 6 flanking polymorphic DNA markers showed that the affection is transmitted, through the carrier daughters to the grandsons and the greatgrandsons and that the great-grandfather is a transmitting male. This observation led us to question the importance of these clinically normal males, who are nonexpressing carriers and termed transmitting males. One propositus, described as a mentally retarded young man, had inherited identical restriction polymorphisms from his mother. Chromosome analysis showed a Klinefelter syndrome, with a fragile site in 18% of the cells leading to the conclusion that the nondisjunction occurred at the first stage of the maternal meiosis.