Loesch D Z, Hay D A, Mulley J
Department of Psychology, La Trobe University, Melbourne, Australia.
Am J Med Genet. 1994 Jul 15;51(4):392-9. doi: 10.1002/ajmg.1320510418.
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)
脆性X综合征“传递男性”通常被定义为表型正常的半合子，他们很少或没有脆性位点，并且将脆性X前突变传递给表型正常的女儿。然而，这一定义缺乏客观依据。作为脆性X综合征遗传基础的不稳定CCG重复序列的发现，进一步强调了具有短重复序列且FMR1基因表达正常的“正常传递男性”与具有较大重复序列（δ>0.6 kb）且完全缺乏FMR1转录的受影响男性之间的明显差异。我们最近表明，脆性X综合征表型表达中这两组之间的转变是渐进的，主要是由于甲基化镶嵌现象。然而，关于短重复序列（0.0<δ<0.6）范围内的表型数据不足。在本文中，我们通过比较正常传递男性样本与其非脆性X男性亲属的一些临床、人体测量和心理测量数据来解决这个问题。此外，还将短重复序列的女性携带者与其非脆性X女性亲属的相同特征进行了比较。结果表明，短重复序列的男性和女性在多项心理测量和身体测量方面与正常人有显著差异，只有男性在典型面部特征上表现出差异。在能够为临床发现提供遗传学解释之前，需要对短重复序列范围内的基因型-表型相关性进行进一步研究，包括FMR1基因功能的评估和重复序列大小的更精确估计。（摘要截选至250字）
