Department of Life Sciences, Chung Shan Medical University, No 110, Sec 1 Chien-Kuo North Road, Taichung 402, Taiwan
Correspondence: E-mail: kmh{at}csmu.edu.tw
Dear Sir,
The letter of Dean et al. stated that 16 out of 236 alleles (6.8%) had >18 CTG repeats and that seven out of the 15 men who were found to have larger normal DMPK CTG repeats had fathered previous pregnancies without the help of assisted conception, and thus questioned the correlation between idiopathic azoospermia and larger normal DMPK CTG repeats. I think they may have misunderstood the main points we have addressed in our report, including (i) the frequencies of large normal trinucleotide repeats in AR, DMPK, and MJD loci are significantly higher in idiopathic azoospermias than in normal controls, (ii) although most azoospermia patients with large normal alleles (ANs) in the AR, DM1, or MJD loci also had large ANs at certain other loci, the increase in repeat length was not universal, (iii) the application of ICSI in the treatment of azoospermia patients should be undertaken only after thorough genetic evaluation and screening, all of which were clearly stated in discussion section. I am not surprised about their finding, because even male DM patients could have offspring. Although it has been shown that DM patients may have decreased sperm function (Hortas et al., 2000), it does not mean that all males with large normal or expanded CTG repeats at the DM1 locus are infertile. Therefore, it is possible that normal males with proven fertility have large normal CTG repeats. In fact, it has been shown (Davies et al., 1992
) that the frequency of large normal CTG alleles in the normal European population is
11.5%. Likewise, large normal CTG alleles are not exclusive to idiopathic azoospermias. Although no male proven to be fertile in our controls had large CTG repeats (due to the low frequency of large normal alleles in the Taiwanese population), and a subset of idiopathic azoospermias was found to have large normal alleles, we did not suggest that large normal alleles are exclusive to idiopathic azoospermias as mentioned in the letter.
References
Davies, J., Yamagata, H., Shelbourne, P., Buxton, J., Ogihara, T, Nokelainen, P., Nakagawa, M., Williamson, R., Johnson, K. and Miki, T. (1992) Comparison of the myotonic dystrophy associated CTG repeat in European and Japanese populations. J. Med. Genet., 29, 766769.[Abstract]
Hortas, M.L., Castilla, J.A., Gil, M.T., Molina, J., Garrido, M.L., Morell, M. and Redondo, M. (2000) Decreased sperm function of patients with myotonic muscular dystrophy. Hum. Reprod., 15, 445448.