Volume 28, Issue 1 (3-2025)
J Arak Uni Med Sci 2025, 28(1): 78-83 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Hekmatpou P, Hekmatpou P, Jalali Mashayekhi F, Bayat S, Gholami M. Identification of Pathogenic Mutation c.286dupA in TYR Gene in an Individual with Oculocutaneous Albinism Using Exome Sequencing. J Arak Uni Med Sci 2025; 28 (1) :78-83
URL: http://jams.arakmu.ac.ir/article-1-7912-en.html
URL: http://jams.arakmu.ac.ir/article-1-7912-en.html
1- Department of Biology, School of Science, University of Guilan, Rasht, Iran , partohekmatpou@gmail.com
2- Department of Genetics, School of Biological Sciences, Tehran North Branch, Islamic Azad University, Tehran, Iran
3- Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Iran
2- Department of Genetics, School of Biological Sciences, Tehran North Branch, Islamic Azad University, Tehran, Iran
3- Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Iran
Abstract: (266 Views)
Introduction: Oculocutaneous Albinism is a hereditary disease with an autosomal recessive pattern. The incidence of this disease is about 1 in every 17 thousand births. Most of the affected people in Iran are the result of consanguineous marriages. White hair, fair skin, and reduction of iris pigments are the main manifestations of this disease. Also, exposure to sunlight increases the susceptibility of these patients to skin cancer. This study aimed to investigate the genetic cause of a person with Oculocutaneous Albinism by whole exome sequencing.
Methods: A 6cc peripheral blood sample was obtained from a child with oculocutaneous Albinism with an autosomal recessive inheritance pattern. DNA extraction and whole exome sequencing were performed. After analyzing the exome sequencing data, the pathogenic mutation was identified. Then, the Sanger sequencing method was used to confirm and segregate.
Results: The affected case showed homozygous pathogenic mutation (NM_000372.5): c.286dupA p.(Met96AsnfsTer73) in exon 1 of the TYR gene. Oculocutaneous albinism IA was determined according to the mutated gene. Also, the parents of the affected person were heterozygous for the mutation.
Conclusions: The mutation causing oculocutaneous albinism was identified in the affected person using the high-efficiency whole exome sequencing method and then confirming the mutation through Sanger sequencing. Considering the parents' consanguineous marriage of the parents, this finding can be used for preventive measures in the future.
Methods: A 6cc peripheral blood sample was obtained from a child with oculocutaneous Albinism with an autosomal recessive inheritance pattern. DNA extraction and whole exome sequencing were performed. After analyzing the exome sequencing data, the pathogenic mutation was identified. Then, the Sanger sequencing method was used to confirm and segregate.
Results: The affected case showed homozygous pathogenic mutation (NM_000372.5): c.286dupA p.(Met96AsnfsTer73) in exon 1 of the TYR gene. Oculocutaneous albinism IA was determined according to the mutated gene. Also, the parents of the affected person were heterozygous for the mutation.
Conclusions: The mutation causing oculocutaneous albinism was identified in the affected person using the high-efficiency whole exome sequencing method and then confirming the mutation through Sanger sequencing. Considering the parents' consanguineous marriage of the parents, this finding can be used for preventive measures in the future.
Type of Study: Original Atricle |
Subject:
Basic Sciences
Received: 2024/12/21 | Accepted: 2025/01/26
Received: 2024/12/21 | Accepted: 2025/01/26
References
1. Marti A, Lasseaux E, Ezzedine K, Léauté‐Labrèze C, Boralevi F, Paya C, et al. Lessons of a day hospital: Comprehensive assessment of patients with albinism in a European setting. Pigment Cell & Melanoma Research. 2018;31(2):318-29. doi: doi:10.1111/pcmr.12651
2. Grønskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis. 2007;2:43. pmid: 17980020 doi: 10.1186/1750-1172-2-43
3. Montoliu L, Grønskov K, Wei AH, Martínez‐García M, Fernández A, Arveiler B, et al. Increasing the complexity: new genes and new types of albinism. Pigment Cell Melanoma Res. 2014;27(1):11-8. pmid: 24066960 doi: 10.1111/pcmr.12167
4. Kromberg JGR. Epidemiology of albinism. In: Albinism in Africa. Elsevier; 2018. p. 57-79. doi: 10.1016/B978-0-12-813316-3.00003-9
5. Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, et al. Oculocutaneous Albinism Type 1. [May 16, 2013]. Available from: https://ab-expereince.info/wp-content/uploads/2014/04/Oculocutaneous-Albinism-Type-1-GeneReviews%c2%ae-NCBI-Bookshelf.htm
6. Shakil M, Akbar A, Aisha NM, Hussain I, Ullah MI, Atif M, et al. Delineating novel and known pathogenic variants in TYR, OCA2 and HPS-1 genes in eight oculocutaneous albinism (OCA) Pakistani families. Genes (Basel). 2022;13(3):503. pmid: 35328057 doi: 10.3390/genes13030503
7. Mauri L, Manfredini E, Del Longo A, Veniani E, Scarcello M, Terrana R, et al. Clinical evaluation and molecular screening of a large consecutive series of albino patients. J Hum Genet. 2017;62(2):277-90.
8. Preising MN, Forster H, Gonser M, Lorenz B. Screening of TYR, OCA2, GPR143, and MC1R in patients with congenital nystagmus, macular hypoplasia, and fundus hypopigmentation indicating albinism. Mol Vis. 2011;17:939-48. pmid: 21541274
9. Park HY, Gilchrest BA. Signaling pathways mediating melanogenesis. Cell Mol Biol (Noisy-le-grand). 1999;45(7):919-30. pmid: 10643996
10. Fryer JP, Oetting WS, Brott MJ, King RA. Alternative splicing of the tyrosinase gene transcript in normal human melanocytes and lymphocytes. J Invest Dermatol. 2001;117(5):1261-5. pmid: 11710942 doi: 10.1046/j.0022-202x.2001.01549.x
11. Dhangar S, Panchal P, Ghatanatti J, Suralkar J, Shah A, Vundinti BR. Novel deletion of exon 3 in TYR gene causing Oculocutaneous albinism 1B in an Indian family along with intellectual disability associated with chromosomal copy number variations. BMC medical genomics. BMC Med Genomics. 2022;15(1):2. pmid: 34980106 doi: 10.1186/s12920-021-01152-1
12. Deilamani FK, Akbari MT. Potential founder effect of tyrosinase gene mutations in oculocutaneous albinism families from west of Iran. Journal of Human Genetics and Genomics. 2017;1(1). doi:10.5812/jhgg.63718
13. Oetting WS, Mentink MM, Summers CG, Lewis RA, White JG, King RA. Three different frameshift mutations of the tyrosinase gene in type IA oculocutaneous albinism. Am J Hum Genet. 1991;49(1):199. pmid: 1905879
14. Shakil M, Harlalka GV, Ali S, Lin S, D’Atri I, Hussain S, et al. Tyrosinase (TYR) gene sequencing and literature review reveals recurrent mutations and multiple population founder gene mutations as causative of oculocutaneous albinism (OCA) in Pakistani families. Eye (Lond). 2019;33(8):1339-46. pmid: 30996339 doi: 10.1038/s41433-019-0436-9
15. Bibi N, Ullah A, Darwesh L, Khan W, Khan T, Ullah K, et al. Identification and computational analysis of novel TYR and SLC45A2 gene mutations in pakistani families with identical non-syndromic oculocutaneous albinism. Front Genet. 2020;11:749. pmid: 32849781 doi: 10.3389/fgene.2020.00749
16. Si S, Jia X, Xu L, Qin Q, Wu J, Ji W, et al. Identification and characterization of the compound heterozygous variants of TYR gene in a northern Chinese family with Oculocutaneous albinism type 1. Pigment Cell Melanoma Res. 2023;36(6):472-80. pmid: 37403904 doi: 10.1111/pcmr.13111
17. Sun W, Shen Y, Shan S, Han L, Li Y, Zhou Z, et al. Identification of TYR mutations in patients with oculocutaneous albinism. Mol Med Rep. 2018;17(6):8409-13. pmid: 29658579 doi: 10.3892/mmr.2018.8881
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
