SEGREGATION OF FRAXE IN A LARGE FAMILY - CLINICAL, PSYCHOMETRIC, CYTOGENETIC, AND MOLECULAR-DATA

During an ongoing study on X-linked mental retardation, we ascertained a large family in which mild mental retardation was cosegregating wit h a fragile site at Xq27-28. Clinical, psychometric, cytogenetic, and molecular studies were performed. Apart from mild mental retardation, affected males and females did not show a specific clinical phenotype. Psychometric assessment of four representative affected individuals r evealed low academic achievements, with verbal and performance IQs of 61-75 and 70-82, respectively. Cytogenetically the fragile site was al ways present in affected males and was not always present in affected females. With FISH the fragile site was located within the FRAXE regio n. The expanded GCC repeat of FRAXE was seen in affected males and fem ales either as a discrete band or as a broad smear. No expansion was s een in unaffected males, whereas three unaffected females did have an enlarged GCC repeat. Maternal transmission of FRAXE may lead to expans ion or contraction of the GCC repeat length, whereas in all cases of p aternal transmission contraction was seen. In striking contrast to the situation in fragile X syndrome, affected males may have affected dau ghters. In addition, there appears to be no premutation of the FRAXE G CC repeat, since in the family studied here al males lacking the norma l allele were found to be affected.