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

Abstract

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.

Paternal nondisjunction in a 47,XY,fra(X)

“…Parental origin studies have been reported in six of the previous cases [Filippi et al, 1988;Kupke et al, 1991;Schnur et al, 1986;Voeckel et al, 1991], and only one of those showed paternal nondisjunction [Schnur et al, 1986]. Our case adds to the presumption that the combination of Klinefelter syndrome and fragile X syndrome is not a result of the maternal carrier state predisposing to nondisjunction but pure coincidence.…”

“…So far at least 14 cases with 47,XY,fra(X) have been reported [Filippi et al, 1988;Froster-Iskenius et al, 1982;Fryns et al, 1983Fryns et al, , 1988Kleczkowska et al, 1988;Kupke et al, 1991;Mavrou et al, 1988;Pueschel et al, 1987;Voeckel et al, 1991]. Parental origin studies have been reported in six of the previous cases [Filippi et al, 1988;Kupke et al, 1991;Schnur et al, 1986;Voeckel et al, 1991], and only one of those showed paternal nondisjunction [Schnur et al, 1986].…”

The fragile X syndrome.

“…:, t. "': 132 133 The combined results of studies from England, the United States, Australia, and The Netherlands (table 3), irrespective of methodological differences, showed, in a total of 4670 mentally retarded subjects, 30 (0.6%) newly diagnosed fragile X patients.38 133 138 In the general population, a premutation carrier frequency among females of ±1/250 has been observed. '38 1 4 This reflects the proportional excess of relatively stable premutation sized alleles over full mutation alleles.…”