title: An unusual fragile X sibship: female compound heterozygote and male with a partially methylated full mutation.
abstract: 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.
authors.affiliation: Molecular Biology Laboratory, Auxological Italian Institute, and University of Milan, Italy. biomol@auxologico.it
authors.forename: S
authors.initials: S
authors.lastname: Russo
authors.forename: V
authors.initials: V
authors.lastname: Briscioli
authors.forename: F
authors.initials: F
authors.lastname: Cogliati
authors.forename: M
authors.initials: M
authors.lastname: Macchi
authors.forename: F
authors.initials: F
authors.lastname: Lalatta
authors.forename: L
authors.initials: L
authors.lastname: Larizza
mesh_terms: D002873:Chromosome Fragility; D003582:Cytogenetics; D004247:DNA / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007360:Intelligence; D007361:Intelligence Tests; D008297:Male; D008745:Methylation; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009483:Neuropsychological Tests; D009679:Nuclear Family; D010375:Pedigree; D016601:RNA-Binding Proteins; D012737:Sex Factors; D019680:Trinucleotide Repeat Expansion; D014960:X Chromosome / Q000235:genetics
chemical_list: D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human