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

Clin Genet. 1998 Oct;54(4):309-14. doi: 10.1034/j.1399-0004.1998.5440408.x.

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.

MeSH terms

  • Chromosome Fragility
  • Cytogenetics
  • DNA / analysis
  • DNA / genetics
  • DNA / metabolism
  • Female
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Heterozygote
  • Humans
  • Intelligence
  • Intelligence Tests
  • Male
  • Methylation
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Neuropsychological Tests
  • Nuclear Family*
  • Pedigree
  • RNA-Binding Proteins*
  • Sex Factors
  • Trinucleotide Repeat Expansion
  • X Chromosome / genetics

Substances

  • FMR1 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein
  • DNA