Reply to Drs. Dreesen, Smits, and Brunner

✍ Scribed by Willems, Patrick J. ;van Roy, Bernadette ;Raeymaekers, Peter ;Oostra, Ben

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 85 KB
• Volume: 40
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/ajmg.1320400433

✦ Synopsis

In Van Roy et al. [19901 we presented two brothers with mental retardation discordant for the fra(X) syndrome. As both brothers inherited a different X-chromo-soma1 haplotype for several DNA markers flanking the fra(X) gene, we concluded that the risk that the mentally retarded brother without expression of the fra(X) trait had inherited the fra(X) gene was less than 1%.

In their Letter to the Editor, Dreesen et al. [19901 recalculated this probability and arrived at a risk of 3.5%. The discrepancy between our original calculations and those made by Dreesen et al. (1990) is due to the fact that the latter authors could not use all the data that were available to us and did not take into account the high mutation rate of the fra(X) syndrome. As DNA from the maternal grandfather was available, accurate phase determination was possible, in contrast to what Dreesen et al. [19901 state. If we recalculate the risk with the computer program MLINK [Lathrop and Lalouel, 19841, using the penetrance and gene frequency given by Dreesen et al. [19901 and the new mutation rate of 1/3000 [Brown, 19901, we arrive at a risk of 0.9%. Therefore the conclusion made in our original article is indeed valid.

To completely reassure Dreesen et al. [19911 we have run additional DNA markers that map closer to the fra(X) gene than the ones described in our original article. Both brothers have inherited different alleles for the VK21C and VK23 markers which are the closest markers flanking the fra(X) gene described until now. Furthermore, they have different alleles for a CA-repeat VNTR marker which is less than 500 kb away from the putative fra(X) gene .

Taking into account these data, the possibility that both mentally retarded brothers inherited the fra(X) gene is practically zero, which reinforces our initial conclusion.