Abstract Oculocutaneous albinism (OCA) is a disorder of defective melanin biosynthesis that is characterized by hypo- pigmentation of skin, hair and retinal pigment epithelium. Phenotypically, OCA patients exhibit white milky skin, whitish to golden hair and deterioration of retinal cells. Until recently, genetic studies have reported seven causative genes (TYR, TYRP1, OCA2, SLC45A2, SLC24A2, C10ORF11 and MCIR) and an uncharacterized OCA5 locus. Herein we present the medico-genetic study of three Pakistani patients inheriting autosomal recessive OCA. Whole exome sequencing, followed by Sanger DNA sequencing for segregation analysis, revealed recurrent mutations c.346C>T (p.Arg116*) and c.1255G>A (p.Gly419Arg) (family A and B respectively) in TYR gene, while the patient from family C did not reveal any known gene mutation, which suggests the involvement of some novel genetic factor. It is the first report of mapping c.346C>T mutation in a Pakistani patient. Our study further extends the evidence of genetic hotspots regions in TYR gene causing OCA in Pakistani population. Keyword: Oculocutaneous albinism, exome sequencing, genetic analysis, TYR gene Introduction Oculocutaneous albinism (OCA) is a pigmentary disorder of defective melanin biosynthesis pathway that is manifested by hypo-pigmentation of skin, hair and retinal pigment epithelium. The clinical features of OCA patients comprise of white milky skin, whitish to golden hair and deterioration of retinal cells. The ophthalmologic consequences in OCA patients usually include photophobia, nystagmus, low visual acuity, Rod and Cone cell deterioration, fovea hypoplasia and misrouting of the optic nerves at the chiasma. 1 OCA is a genetically heterogeneous disorder, which mostly segregates in an autosomal recessive manner. Until now, seven genes (TYR, TYRP1, OCA2, SLC45A2, SLC24A2, C10ORF11 and MC1R) and an uncharacterized OCA5 locus have been mapped on the human genome. 2 At molecular level, these OCA protein products are involved in melanin metabolism and transport. Epidemiologic studies of Europe and United States indicated that genetically caused OCA affects 1 in 17000 newborns, while this figure may be higher in Pakistani society where rate of consanguineous marriages are over 60 % among which the ratio of first cousin union is found in 80% of couples. 3 Here in this study, we report on two recurrent mutations in TYR gene, in which c.346C>T is mapped first time in a Pakistani patient. Our study supports the evidence of mutational hotspots in TYR gene causing OCA in Pakistani patients. CaseReport In this presented investigative study, we ascertained four Vol. 67, No. 5, May 2017 790 CASE REPORT Ophthalmo-genetic analysis of Pakistani patients with nonsyndromic oculocutaneous albinism through whole exome sequencing Hadia Gul, 1 Muhammad Zeeshan Ali, 2 Ejazullah Khan, 3 Muhammad Zubair, 4 Muhammad Badar, 5 Saadullah Khan, 6 Abdul Haleem Shah, 7 Muzammil Ahmad Khan 8 1,7 Department of Biological Sciences, Faculty of Sciences, 2,3,5,8 Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan, KPK, Pakistan, 4 Department of Cell and Developmental Biology, School of Life Sciences, University of Science and Technology, China, 6 Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, KPK, Pakistan. Correspondence: Muzammil Ahmad Khan. Email: m.ahmad@gu.edu.pk Table: The clinical spectrum of OCA patients from family A, B and C. Phenotypic feature Family A Family B Family C [c.346C>T [c.1255G>A Novel plausible (p.Arg116*)] (p.G419R)] variants Hair colour White White Golden Skin colour White White White with Redish shade Iris colour Blue Blue Brown Eye Sight Weak Weak Weak Photophobia Yes Yes Yes Nystagmus Yes Yes Yes Strabismus No No Yes Cataract No No No Keratoconus No No No Colour blindness No No No Impaired StereoscopicVision No No Minor impairment Depth perception Minor Minor Moderate Reduction Reduction Reduction Hearing impairment No No No Over weight No No No Wide tooth spacing No No No