title: Transmitting males and carrier females in fragile X--revisited.
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)
authors.affiliation: Department of Psychology, La Trobe University, Melbourne, Australia.
authors.forename: D Z
authors.initials: DZ
authors.lastname: Loesch
authors.forename: D A
authors.initials: DA
authors.lastname: Hay
authors.forename: J
authors.initials: J
authors.lastname: Mulley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D002648:Child; D004247:DNA / Q000378:metabolism; D005145:Face / Q000002:abnormalities; D005192:Family Health; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D005796:Genes; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008745:Methylation; D008875:Middle Aged; D008957:Models, Genetic; D009030:Mosaicism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D010641:Phenotype; D011594:Psychometrics; D016601:RNA-Binding Proteins; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
chemical_list: D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human