Wilhelm D, Froster-Iskenius U, Paul J, Schwinger E
Institut für Humangenetik, Medizinische Universität, Federal Republic of Germany.
Am J Med Genet. 1988 May-Jun;30(1-2):407-15. doi: 10.1002/ajmg.1320300141.
Female heterozygotes of the fra(X) form of mental retardation show variable degrees of mental impairment and phenotype expression of the disorder. This might be an effect of inactivation of the X-chromosome which carries the fra(X)(q). Prior replication studies in heterozygous carriers gave contradictory results with respect to possible genotype-phenotype correlation. In the interpretation of these studies it is important to understand the effect of BrdU on the fra(X)(q) expression. In a group of 13 hemizygous patients with fra(X)(q) and 7 heterozygous carriers we studied the effect of BrdU on fra(X) expression. In the heterozygous carriers the use of BrdU resulted in a significant suppression of the fra(X)(q), while in hemizygous patients no difference in fra(X)(q) frequency with or without BrdU could be observed. It can be concluded that BrdU suppresses the fra(X)(q) preferentially on the inactive X-chromosome. Thus the fra(X)(q) frequency on the active X-chromosome is of primary importance in phenotype correlation studies among heterozygous carriers. In our group of heterozygous carriers we observed a negative correlation between (IQ) phenotype and fra(X)(q) expression on the active X-chromosome. This suggests that the gene for the fra(X)(q) form of mental retardation is on the X-chromosome and undergoes inactivation.
脆性X染色体型智力障碍的女性杂合子表现出不同程度的智力损害和该疾病的表型表达。这可能是携带脆性X染色体（q）的X染色体失活的结果。先前对杂合子携带者的复制研究在可能的基因型-表型相关性方面给出了相互矛盾的结果。在解释这些研究时，了解5-溴脱氧尿苷（BrdU）对脆性X染色体（q）表达的影响很重要。在一组13名患有脆性X染色体（q）的半合子患者和7名杂合子携带者中，我们研究了BrdU对脆性X染色体表达的影响。在杂合子携带者中，使用BrdU导致脆性X染色体（q）显著抑制，而在半合子患者中，无论有无BrdU，脆性X染色体（q）频率均未观察到差异。可以得出结论，BrdU优先抑制失活X染色体上的脆性X染色体（q）。因此，在杂合子携带者的表型相关性研究中，活性X染色体上的脆性X染色体（q）频率至关重要。在我们的杂合子携带者组中，我们观察到（智商）表型与活性X染色体上的脆性X染色体（q）表达之间呈负相关。这表明脆性X染色体型智力障碍的基因位于X染色体上并发生失活。
