Comment on homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene

Dear Editor,

I have carefully read the article entitled “Homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene”, published by Shakil et al[1] in 2016 and found it very interesting for the scientific community. I will consider it a significant contribution of authors toward the development of molecular diagnosis and better management of oculocutaneous albinism(OCA). In that article, Shakil et al[1] analyzed 10 Pakistani families with OCA and determine the association of one AL03 family with TYR locus, while rest of the families were excluded from the known OCA loci and suggest the involvement of novel genetic factors in disease etiology.

I fully agree with the medico-genetic outcomes of the present study. However, with due respect, I have few technical concerns that I believe will further improve this article and make it interesting for the readers. My first concern is regarding the title of this article “Homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene”, which reveals that they analyzed single OCA family, while in the text body authors have described that they screened 10 families (see also conclusion).My second concern is regarding the linkage analysis of family AL03, which shows two point logarithm of odd (LOD) score of 1.80 at marker D11S1367 at zero recombination fraction.In statistical term, for association of a locus with disease phenotype (autosomal recessive) the LOD score should be 3.0 at zero recombination fraction, while the current analysis does not meet the statistical criteria of linkage analysis.Nevertheless, the LOD score can be regarded as suggestive of linkage to disease. Moreover, they did not perform sequence analysis of TYR gene for mutation identification. Given the low value of LOD score (less than 3) and no mutation analysis may reduce the significance of TYR gene linkage to disease phenotype.

However, I would like to add few minor suggestions to this commentary regarding the linkage and mutation analysis of AL03 family associated with TYR gene locus. In order to positively justify the suggestive LOD score value, author should perform simulation analysis to determine the total linkage power of this family and then compare the actual LOD value with simulated value, which should come close to each other. Or, they can achieve signif i cant LOD score of 3 by enrolling additional affected individuals from fi fth generation(V-1 and V-2). Regarding the sequence analysis, the authors should consider the sequencing of few common TYR gene mutations that are reported by Jaworek et al[2] in Punjabi ethnic Pakistani families. Mutation analysis of the TYR gene in AL03 family will be their significant contribution in personalized healthcare and devising an ethnic specif i c molecular diagnostic test for genetic counseling of Pakistani families.

ACKNOWLEDGEMENTS

Conf l icts of Interest: Khan MA, None.

REFERENCES

1 Shakil M, Ullah MI, Hussain S, Firasat S, Mahmood S, Kaul H.Homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene. Int J Ophthalmol 2016;9(5):794-796.

2 Jaworek TJ, Kausar T, Bell SM, Tariq N, Maqsood MI, Sohail A, Ali M, Iqbal F, Rasool S, Riazuddin S, Shaikh RS, Ahmed ZM. Molecular genetic studies and delineation of the oculocutaneous albinism phenotype in the Pakistani popula tion. Orphanet J Rare Dis 2012;7:44.