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Identification of two Missense Mutations (p.Ile198Thr & p.Ser44Arg) in TYR gene in Pakistani families

By: Muhammad Luqman, Asma Yousafzai, Nisar Ahmed, Asad Ullah, Riaz-ul-Amin, Abdul Hameed Baloch, Sara Naudhani, Shakeela Daud

Key Words: Oculocutaneous albinism, Tyrosinase, Mutational analysis

Int. J. Biosci. 10(4), 232-238, April 2017.



Oculocutaneous albinism (OCA) is an autosomal recessive disorder. The most common type oculocutaneous albinism type 1 (OCA1) is caused by tyrosinase (TYR) gene. Biosynthesis of melanin in human are controlled by Tyrosinase enzyme, which is encoded by gene TYR present on 11q14.3 chromosome. TYR gene is expressed in melacocytes typically in the skin. A majority of TYR mutations deactivates tyrosinase to impair the capability of melanocytes to produce melanin life time. People with this form of albinism have white hair, light-colored eyes, and very pale skin. Some of the TYR mutations do not completely deactivate tyrosinase and melanocytes do produce some the melanin, cause OCA1B (MIM# 606952). In the current study a total of five families containing two or more affected individuals with oculocutaneous albinism (OCA) were enrolled. Clinical symptoms were recorded and pedigrees were drawn by visiting these families. Blood samples (5cc) were also collected from all affected individuals, their normal siblings and parents in EDTA containing falcon tubes. Genomic DNA was extracted using inorganic method. Linkage analysis was performed by three STR markers D11S1780, D11S1367 and D11S4175. Two families showed linkage to OCA1. Sequence analysis of exons and flanking intronic regions was performed for TYR gene. Two known missense mutations (p.Ile198Thr & p.Ser44Arg) causing oculocutaneous albinism type 1 were identified, whereas sequence analysis of normal individuals has shown no sequence change in respective codons. The current study is very important which confirms important mutations causing oculocutaneous albinism in Pakistani families.

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Identification of two Missense Mutations (p.Ile198Thr & p.Ser44Arg) in TYR gene in Pakistani families

Ando H, Kondoh H, Ichihashi M, Hearing VJ. 2007. Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. The Journal of Investigative Dermatology 127(4), 751–61.

Budisteanu M, Arghir A, Chirieac SM, Cardos G, Lungeanu A. 2010. Oculocutaneous albinism associated with multiple malformations and psychomotor retardation. Pediatric Dermatology 27, 212–214.

Chen K, Manga P, Orlow SJ. 2002. Pink-eyed dilution protein controlsthe processing of tyrosinase. Molecular Biology of the Cell 13, 1953–64.

Forshew T, Khaliq S, Tee L, Smith U, Johnson CA, Mehdi SQ, Maher ER. 2005. Identification of novel TYR and TYRP1 mutations in oculocutaneous albinism. Clinical Genetics 68, 182–184.

Giebel LB, Tripathi RK, King RA, Spritz RA. 1991. A tyrosinase gene missense mutation in temperature-sensitive type I oculocutaneous albinism. A human homologue to the Siamese cat and the Himalayan mouse. Journal of Clinical Investigation 87, 1119–1122.

Goto M, Sato-Matsumura KC, Sawamura D, Yokota K, Nakamura H, Shimizu H. 2004. Tyrosinase gene analysis in Japanese patients with oculocutaneous albinism. Journal of  Dermatoogical Science 35, 215–220.

Grimberg J, Nawoschik S, Belluscio L, McKee R, Turck A, Eisenberg A. 1989. A simple and efficient non-organic procedure for the isolation of genomic DNA from blood. Nucleic Acids Research 17(20), 8390.

Inagaki K, Suzuki T, Shimizu H. 2004.  Oculocutaneous albinism type 4 is one of the most common types of albinism in Japan. American Journal of Human Genetics 74, 466–471.

Jaworek TJ, Kausar T, Bell SM, Tariq N, Maqsood MI, Sohail A, Ali M, Iqbal F, Rasool S, Riazuddin S, Shaikh RS, Ahmed ZM. 2012. Molecular genetic studies and delineation of the oculocutaneous albinism phenotype in the Pakistani population. Orphanet Journal of Rare Diseases 26(7), 44.

Kausar T, Jaworek TJ, Tariq N, Sadia S, Ali M, Shaikh RS, Ahmed ZM. 2013. Genetic studies of TYRP1 and SLC45A2 in Pakistani patients with nonsyndromic oculocutaneous albinism. Journal of Investigational Dermatology 133, 1099-1102.

Kikuchi H, Hara S, Ishiguro S, Tamai M, Watanabe M. 1990. Detection of point mutation in the tyrosinase gene of a Japanese albino patient by a direct sequencing of amplified DNA. Human Genetics 85, 123-124.

Kumar CM, Sathisha UV, Dharmesh S, Rao AG, Singh SA. 2011. Interaction of sesamol (3,4-methylenedioxyphenol) with tyrosinase and its effect on melanin synthesis. Biochimie 93(3), 562–9. 21144881.

Manga P, Kromberg J, Turner A. 2001. In Southern Africa, brown oculocutaneous albinism (BOCA) maps to the OCA2 locus on chromosome 15q: P-gene mutations identified. American Journal of Human Genetics 68, 782–787.

Nakamura E, Miyamura Y, Matsunaga J, Kano Y, Dakeishi-Hara M, Tanita M, Kono M, Tomita Y. 2002. A novel mutation of the tyrosinase gene causing oculocutaneous albinism type 1 (OCA1). Journal of Dermatoogicall Science 28, 102-105.

Oetting WS, King RA. 1992. Molecular analysis of type I-A (tyrosinase negative) oculocutaneous albinism. Hum Genetics 90, 258–262.

Opitz S, Käsmann-Kellner B, Kaufmann M, Schwinger E, Zühlke C. 2004. Detection of 53 novel DNA variations within the tyrosinase gene and accumulation of mutations in 17 patients with albinism. Human Mutation 23, 630-631.

Park KC, Park SK, Lee YS. 1996. Mutations of the tyrosinase gene in three Korean patients with type I oculocutaneous albinism. Japanese Journal of Human Genetics 41, 299–305.

Passmore LA, Kaesmann-Kellner B, Weber BH. 1999. Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population. Human Genetics 105, 200–210.

Puri N, Gardner JM, Brilliant MH. 2000. Aberrant pH of melanosomes in pink-eyed dilution (p) mutant melanocytes. Journal of Investigative Dermatology 115, 607–613.

Rooryck C, Roudaut C, Robine E, Musebeck J, Arveiler B. 2006. Oculocutaneous albinism with TYRP1 gene mutations in a Caucasian patient. Pigment Cell Research 19, 239–242.

Seven M, Yosunkaya E, Yilmaz SB, Karaca E, Guven G, Yuksel A. 2011. A new syndrome presenting with dysmorphic facies, oculocutaneous albinism, glaucoma, cryptorchidism and mental retardation. Genetic Counselling 22, 25–34.

Shah SA, Din SU, Raheem N, Daud S, Mubeen J, Nadeem A, Tayyab M, Baloch DM, Babar MS, Ahmad J. 2014. Identification of a novel mutation (p.Ile198Thr) in gene TYR in a Pakistani family with nonsyndromic oculocutaneous albinism. Clinical and Experimental Dermatology 39, 646–648.

Simeonov D, Wang X, Wang C, Sergeev Y, Dolinska M, Bower M, Fischer R, Winer D, Dubrovsky G, Balog J, Huizing M, Hart R, Zein W, Gahl W, Brooks B, Adams D. 2013. DNA Variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics. Human Mutation 34, 827-35.

Spritz RA. 1993. Molecular genetics of oculocutaneous albinism. Semin Dermatol 12, 167-172.

Stokowski RP, Pant PV, Dadd T, Fereday A, Hinds DA, Jarman C, Filsell W, Ginger RS, Green MR, Van der Ouderaa FJ, Cox DR. 2007. A genomewide association study of skin pigmentation in a South Asian population. American Journal of Human Genetics 81, 1119-1132.

Suzuki T, Miyamura Y, Matsunaga J. 2003. Six novel P gene mutations and oculocutaneous albinism type 2 frequency in Japanese albino patients. Journal of Investigative Dermatology 120, 781–783.

Tatusova TA, Madden TL. 1999.  BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences. FEMS Microbiology Letter 174, 247-250.

Tripathi RK, Bundey S, Musarella MA, Droetto S, Strunk KM, Holmes SA, Spritz RA. 1993. Mutations of the tyrosinase gene in Indo-Pakistani patients with type I (tyrosinase-deficient) oculocutaneous albinism (OCA). American Journal of Human Genetics 53, 1173–1179.

Tripathi RK, Hearing VJ, Urabe K, Aroca P, Spritz RA. 1992. Mutational mapping of the catalytic activities of human tyrosinase. Journal of Biological Chemistry 267, 23707–23712.

Muhammad Luqman, Asma Yousafzai, Nisar Ahmed, Asad Ullah, Riaz-ul-Amin, Abdul Hameed Baloch, Sara Naudhani, Shakeela Daud. 2017. Identification of two Missense Mutations (p.Ile198Thr & p.Ser44Arg) in TYR gene in Pakistani families. Int. J. Biosci. 10(4), 232-238.
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