Transmitting males and carrier females in fragile X--revisited

Am J Med Genet. 1994 Jul 15;51(4):392-9. doi: 10.1002/ajmg.1320510418.

Abstract

Fragile X "transmitting males" have customarily been defined as phenotypically normal hemizygotes, who show very few or no fragile sites, and who transmit the fragile X premutation to phenotypically normal daughters. However, an objective justification of this definition was lacking. The discovery of an unstable CCG repeat as the genetic basis of fragile X further emphasized the apparent distinction between the "normal transmitting males" with short repeat and expression of the FMR1 gene, and the affected males with larger repeats (delta > 0.6 kb) and a complete lack of FMR1 transcription. We have recently shown that the transition between these two groups in phenotypic expression of fragile X is gradual, mainly on account of methylation mosaicism. However, there were insufficient data on the phenotype within the short repeat (0.0 < delta < 0.6) range. In this paper we approach this problem by comparing some clinical, anthropometric, and psychometric data from a sample of normal transmitting males with those from their non-fragile X male relatives. Moreover, female carriers with short repeat are compared for the same traits with their non-fragile X female relatives. The results have shown that both males and females with a short repeat differed significantly from normal on several psychometric and physical measurements, and males only showed differences in typical facial traits. Further studies of genotype-phenotype correlations within the short repeat range, including the estimate of FMR1 gene function and a more exact estimate of repeat size, is required before genetic explanation for the clinical findings can be provided.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chi-Square Distribution
  • Child
  • DNA / metabolism
  • Face / abnormalities
  • Family Health
  • Female
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / pathology
  • Gene Expression*
  • Genes
  • Genotype
  • Heterozygote*
  • Humans
  • Likelihood Functions
  • Male
  • Methylation
  • Middle Aged
  • Models, Genetic*
  • Mosaicism
  • Nerve Tissue Proteins / biosynthesis
  • Phenotype
  • Psychometrics
  • RNA-Binding Proteins*
  • Repetitive Sequences, Nucleic Acid
  • Transcription, Genetic

Substances

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