An unusual fragile X sibship: female compound heterozygote and male with a partially methylated full mutation

We describe here a fragile X sibship of borderline retarded sister and brother born to carrier parents. The sister is a compound heterozygote (with a full mutation on one X chromosome and a pre-mutation on the other X chromosome). The brother has a partially methylated full mutation. The activation ratio (AR) for the sister's pre-mutation was 0.69 and the percent lack of methylation for the brother's full mutation was 73%. Intellectual and neuropsychological Wechsler Adult Intelligence Scale (W.A.I.S.) achievement tests reported full scale IQ scores of 74 in the sister and 77 in the brother. A significant discrepancy between verbal and performance IQ was found in the sister, indicating that her main impairment was in the cognitive area. The parents of this unusual sibship came from a small village, as did one of the two previously described cases of compound heterozygous females. These rare females raise special issues for genetic counselling in fragile X carrier couples, the frequency of which remains to be defined in different populations.