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- Published on: 23 August 2019
- Published on: 23 August 2019Response to Monfermé et al., 2018
To the Editor:
We read the recent article in the journal by Monfermé and coauthors (1) on phenotypic associations of TYR R402Q compound heterozygosity with keen interest. Given our own and others previous findings (2-4) that the R402Q-S192Y haplotype seemed to have a stronger biological effect, we were surprised that a triallelic effect was not supported in the clinical discussion by Monfermé et al. When we examined these results more closely, we noted that their sample included 52 S192Y variant allele carriers out of the entire collection of 69 patients, of whom 31 (44.9%) carried the R402Q-S192Y double variant haplotype. In our own collections from the Australian general population (BNMS and BLTS, Duffy et al., in submission), only 6% of R402Q carriers also carried S192Y in cis. When we examined the European 1000 Genomes subsamples, there too only 7% of R402Q haplotypes had the 192Y rather than 192S wild type allele. So, even though Monfermé et al could not detect a statistically significant additive effect on OCA trait severity due to the S192Y polymorphism within their sample, it is clear that the S192 variant allele is markedly overrepresented compared to the general population, suggesting that it must have some relationship to albinism. This genetic association of the TYR R402Q-S192Y double variant haplotype with OCA1 is now clearly causative (2, 3), and explains some of the missing heritability that has previously been seen in OCA patients (4).
Yours,...
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None declared.