Mutational Analysis of TYR Gene Causing Oculocutaneous Albinism in Families from District Peshawar

Oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by either complete lack of or a reduction of melanin biosynthesis in the melanocytes. The OCA1A is the most severe type with a complete lack of melanin production throughout life, while the milder forms OCA1B, OCA2, OCA3, and OCA4 show some pigment accumulation over time. Mutations in TYR, OCA2, TYRP1, and SLC45A2 are mainly responsible for causing oculocutaneous albinism. Recently, two new genes SLC24A5 and C10orf11 are identified that are responsible to cause OCA6 and OCA7, respectively. Also a locus has been mapped to the human chromosome 4q24 region which is responsible for genetic cause of OCA5. In this paper, we summarized the clinical and molecular features of OCA genes. Further, we reviewed the screening of pathological mutations of OCA genes and its molecular mechanism of the protein upon mutation byin silicoapproach. We also reviewed TYR (T373K, N371Y, M370T, and P313R), OCA2 (R305W), TYRP1 (R326H and R356Q) mutations and their structural consequences at molecular level. It is observed that the pathological genetic mutations and their structural and functional significance of OCA genes will aid in development of personalized medicine for albinism patients.

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Potential Founder Effect of Tyrosinase Gene Mutations in Oculocutaneous Albinism Families from West of Iran

Journal of Human Genetics and Genomics ◽

10.5812/jhgg.63718 ◽

2017 ◽

Vol 1 (1) ◽

Author(s):

Faravareh Khordadpoor Deilamani ◽

Mohammad Taghi Akbari

Keyword(s):

Founder Effect ◽

Gene Mutations ◽

Homozygosity Mapping ◽

Oculocutaneous Albinism ◽

Founder Mutations ◽

Single Base ◽

Str Markers ◽

Tyrosinase Gene ◽

Similar Haplotype ◽

Tyr Gene

Background: Non syndromic oculocutaneous albinism type (OCA) is caused by mutations in tyrosinase (TYR), OCA2, TYRP1, MATP (SLC45A2), SLC24A5 and C10ORF11 genes. Screening for mutations is important in families with oculocutaneous albinism patients in order to accurately diagnose the albinism type, genetic counseling and future therapeutic purposes. Objectives: The Aim of this study was to investigate the founder effect of most frequent mutations in OCA patients. Methods: TYR gene was sequenced in 26 unrelated inbred OCA families as well as 56 unrelated healthy individuals. In addition, homozygosity mapping was performed using 13 STR markers for 6 OCA loci (TYR, OCA2, TYRP1, MATP (SLC45A2), SLC24A5 and C10ORF11 genes). Different mutations were found in these genes from which a single base duplication (c.286dupA) and two single base substitutions c.996G > A (p.M332I) and c.230G > A (p.R77Q) had the most frequencies among the OCA families. In order to investigate the founder effect of these mutations, the haplotypes of two STR markers (TYR-S1 and TYR-S2) inside the TYR gene were ascertained. Results: It was revealed that families with similar mutation harbored similar haplotype for the TYR STR markers too. Conclusions: We conclude that these mutations are possible founder mutations in the Iranian population.

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In-silico analysis of deleterious missense SNPs of human TYR gene associated with oculocutaneous albinism type 1 (OCA1)

Meta Gene ◽

10.1016/j.mgene.2020.100674 ◽

2020 ◽

Vol 24 ◽

pp. 100674 ◽

Cited By ~ 2

Author(s):

Malik Siddique Mahmood ◽

Saba Irshad ◽

Tehreem Aqdas Butt ◽

Hina Batool ◽

Sana Batool ◽

...

Keyword(s):

In Silico ◽

In Silico Analysis ◽

Oculocutaneous Albinism ◽

Tyr Gene ◽

Silico Analysis

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Mutational analysis of a Chinese family with oculocutaneous albinism type 2

Oncotarget ◽

10.18632/oncotarget.19697 ◽

2017 ◽

Vol 8 (41) ◽

pp. 70345-70355

Author(s):

Xiong Wang ◽

Yaowu Zhu ◽

Na Shen ◽

Jing Peng ◽

Chunyu Wang ◽

...

Keyword(s):

Mutational Analysis ◽

Oculocutaneous Albinism ◽

Chinese Family

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Two Novel Tyrosinase (TYR) Gene Mutations with Pathogenic Impact on Oculocutaneous Albinism Type 1 (OCA1)

PLoS ONE ◽

10.1371/journal.pone.0106656 ◽

2014 ◽

Vol 9 (9) ◽

pp. e106656 ◽

Cited By ~ 19

Author(s):

Vadieh Ghodsinejad Kalahroudi ◽

Behnam Kamalidehghan ◽

Ahoura Arasteh Kani ◽

Omid Aryani ◽

Mahdi Tondar ◽

...

Keyword(s):

Gene Mutations ◽

Oculocutaneous Albinism ◽

Tyr Gene

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Mutational analysis of TYR gene and its structural consequences in OCA1A

Gene ◽

10.1016/j.gene.2012.09.128 ◽

2013 ◽

Vol 513 (1) ◽

pp. 184-195 ◽

Cited By ~ 36

Author(s):

Balu K ◽

Rituraj Purohit

Keyword(s):

Mutational Analysis ◽

Tyr Gene

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A Novel Deletion Mutation of the TYR Gene in a Patient With Oculocutaneous Albinism Type 1A

Gene Cell and Tissue ◽

10.17795/gct-33678 ◽

2016 ◽

Vol 3 (1) ◽

Author(s):

Farah Talebi ◽

Farideh Ghanbari ◽

Javad Mohammadi Asl

Keyword(s):

Oculocutaneous Albinism ◽

Deletion Mutation ◽

Tyr Gene

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Complex intragene deletion leads to oculocutaneous albinism in tanuki (Japanese raccoon dog)

Genome ◽

10.1139/gen-2020-0049 ◽

2020 ◽

Vol 63 (10) ◽

pp. 517-523

Author(s):

Yuji Mae ◽

Kenji Nagara ◽

Manabu Miyazaki ◽

Yukako Katsura ◽

Yuki Enomoto ◽

...

Keyword(s):

Oculocutaneous Albinism ◽

Nyctereutes Procyonoides ◽

Formation Processes ◽

Copper Binding ◽

Raccoon Dog ◽

Nucleotide Substitutions ◽

The Third ◽

Albino Phenotype ◽

Dna Scission ◽

Tyr Gene

Tanuki (Nyctereutes procyonoides viverrinus), or Japanese raccoon dog, is a canine native to Japan. Tanuki with complete oculocutaneous albinism are relatively frequent in mountainous areas of mainland Japan. Tyrosinase, which is encoded by the TYR gene, is an enzyme essential for the biosynthesis of melanin pigment. We examined the structure and nucleotide sequence of TYR in an albino tanuki and found that the third exon was removed due to a deletion of approximately 11 kb. In addition, two nonsynonymous nucleotide substitutions were found in the fifth exon. These mutations are possible causes of the albino phenotype; however, the order of occurrence is unclear. Even if the 11-kb deletion was not the first of these mutations, it is considered to cause a total loss of the tyrosinase function because the third exon carries codons for one of the two copper-binding sites of tyrosinase and these sites are essential for the enzyme function. Intriguingly, the deletion was not a simple removal of an 11-kb segment: an internal portion was retained as a segment in the reverse orientation. We propose possible formation processes for this mutation that involve multiple DNA scission events, or an inversion followed by a deletion.

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