Unveiling genetics of non-syndromic albinism using whole exome sequencing: A comprehensive study of TYR, TYRP1, OCA2 and MC1R genes in 17 families

被引：3

作者：

Zaman, Qaiser ^{[1
,2
,3
]}

Khan, Jamshid ^{[1
]}

Ahmad, Mashal ^{[1
]}

Khan, Hamza ^{[1
,4
]}

Chaudhary, Hammad Tufail ^{[5
]}

Rehman, Gauhar ^{[3
]}

Rahman, Obaid Ur ^{[6
]}

Shah, Muhammad M. ^{[1
]}

Hussain, Javeria ^{[1
]}

Jamal, Qaisar ^{[7
]}

Khan, Bakht Tareen ^{[7
]}

Khan, Muhammad A. ^{[1
]}

Sadeeda ^{[1
]}

Sahar, Kalsoom ^{[1
]}

Idrees, Muhammad ^{[1
]}

Ahmad, Raees ^{[8
]}

Faisal, Mohammad Shah

Khan, Muhammad Ismail ^{[4
]}

Khisroon, Muhammad ^{[4
,7
]}

Abdulkareem, Angham Abdulrhman ^{[9
,10
]}

Lee, Eugene ^{[11
]}

Ryu, Seung Woo ^{[11
]}

Bibi, Nousheen ^{[12
]}

Muthaffar, Osama Yousef ^{[13
]}

Jelani, Musharraf ^{[14
]}

Naseer, Muhammad Imran ^{[9
,15
]}

机构：

[1] Govt Postgrad Coll Dargai, Dept Zool, Malakand 23050, Pakistan

[2] Govt Khyber Pakhtunkhwa, Higher Educ Dept, Peshawar 25120, Pakistan

[3] Abdul Wali Khan Univ, Dept Zool, Mardan 23200, Pakistan

[4] Islamia Coll Peshawar, Dept Zool, Peshawar 25120, Pakistan

[5] Taif Univ, Coll Med, Dept Pathol, Taif, Saudi Arabia

[6] Swat Med Coll, Dept Biochem, Swat 19200, Pakistan

[7] Univ Peshawar, Dept Zool, Peshawar 25120, Pakistan

[8] Govt Postgrad Coll Timergara, Dept Zool, Dir Lower 18300, Pakistan

[9] King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah, Saudi Arabia

[10] King Abdulaziz Univ, Fac Sci, Dept Biochem, Jeddah, Saudi Arabia

[11] 3Billion Inc, Seoul, South Korea

[12] Shaheed Benazir Bhutto Women Univ, Dept Bioinformat, Peshawar 25120, Pakistan

[13] King Abdulaziz Univ, Fac Med, Dept Pediat, Jeddah, Saudi Arabia

[14] Islamia Coll, Ctr Om Sci, Rare Dis Genet & Genom, Peshawar 25120, Khyber Pakhtunk, Pakistan

[15] King Abdulaziz Univ, Fac Appl Med Sci, Dept Med Lab Technol, Jeddah, Saudi Arabia

来源：

GENE | 2024年 / 894卷

关键词：

Oculocutaneous albinism; Skin depigmentation; Melanocytes; Molecular diagnostics; Whole exome sequencing; OCULOCUTANEOUS ALBINISM; MUTATIONS; OCA1;

D O I：

10.1016/j.gene.2023.147986

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background: Oculocutaneous albinism (OCA) is a group of skin depigmentation disorders. Clinical presentation of OCA includes defects in melanocyte differentiation, melanin biosynthesis, and melanosome maturation and transport.Objectives: A molecular diagnostics study of families presenting oculocutaneous albinism.Methods: In this study, 17 consanguineous OCA families consisting of 93 patients were investigated. Whole Exome Sequencing (WES) of the index patient in each family were performed. Short listed variants of WES were Sanger validated for Mendelian segregation in obligate carriers and other available family members. Variant prioritization and pathogenicity were classified as per the criteria of American College Medical Genetics and Genomics (ACMG). Comparative computational modelling was performed to predict the potential damaging effect of the altered proteins.Results: 15 pathogenic variations: c.132 T > A, c.346C > T, c.488C > G, c.1037G > A in TYR, c.1211C > T, c.1441G > A, c.1706_1707insT, c.2020C > G, c.2402G > C, c.2430del, in OCA2, c.1067G > A in TYRP1 and c.451C > T, c.515G > T, c.766C > T, c.917G > A in MC1R genes were identified. Three variants in OCA2 gene were characterized: c.1706_1707insT, c.2430del, and c.2402G > C, all of which were not reported before in OCA families.Conclusion: A few studies focusing on mutation screening of OCA patients have been reported before; however, this study has uniquely presents the Pakhtun ethnic population residing on the North-Western boarder. It explains that TYR, OCA2, TYRP1, and MC1R variations lead to non-syndromic OCA phenotype The overlapping phenotypes of OCA can precisely be diagnosed for its molecular pathogenicity using WES. This study recommends WES as a first-line molecular diagnostic tool, and provides a basis for developing customized genetic tests i.e. pre-marital screening to reduce the disease burden in the future generations.

引用

页数：9

共 22 条

[1] Whole exome sequencing identified five novel variants in CNTN2, CARS2, ARSA, and CLCN4 leading to epilepsy in consanguineous families [J].

Abdulkareem, Angham Abdulrhman ;

Zaman, Qaiser ;

Khan, Hamza ;

Khan, Sabar ;

Rehman, Gauhar ;

Tariq, Nabeel ;

Ahmad, Mashal ;

Owais, Muhammad ;

Najumuddin, Osama Yousef ;

Muthaffar, Osama Yousef ;

Bibi, Fehmida ;

Khang, Rin ;

Ryu, Seung Woo ;

Naseer, Muhammad Imran ;

Jelani, Musharraf .

FRONTIERS IN GENETICS, 2023, 14

[2] The ACMG/AMP reputable source criteria for the interpretation of sequence variants [J].

Biesecker, Leslie G. ;

Harrison, Steven M. .

GENETICS IN MEDICINE, 2018, 20 (12) :1687-1688

[3]

Chen H., 2006, Atlas Genetic Diagnosis Counseling, P36

[4] Palmitoylation-dependent activation of MC1R prevents melanomagenesis [J].

Chen, Shuyang ;

Zhu, Bo ;

Yin, Chengqian ;

Liu, Wei ;

Han, Changpeng ;

Chen, Baoen ;

Liu, Tongzheng ;

Li, Xin ;

Chen, Xiang ;

Li, Chunying ;

Hu, Limin ;

Zhou, Jun ;

Xu, Zhi-Xiang ;

Gao, Xiumei ;

Wu, Xu ;

Goding, Colin R. ;

Cui, Rutao .

NATURE, 2017, 549 (7672) :399-+

[5] Genetics of non-syndromic and syndromic oculocutaneous albinism in human and mouse [J].

Fernandez, Almudena ;

Hayashi, Masahiro ;

Garrido, Gema ;

Montero, Andrea ;

Guardia, Ana ;

Suzuki, Tamio ;

Montoliu, Lluis .

PIGMENT CELL & MELANOMA RESEARCH, 2021, 34 (04) :786-799

[6] Oculocutaneous albinism [J].

Gronskov, Karen ;

Ek, Jakob ;

Brondum-Nielsen, Karen .

ORPHANET JOURNAL OF RARE DISEASES, 2007, 2 (1)

[7] Comprehensive analysis of oculocutaneous albinism among non-Hispanic Caucasians shows that OCA1 is the most prevalent OCA type [J].

Hutton, Saunie M. ;

Spritz, Richard A. .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2008, 128 (10) :2442-2450

[8] REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants [J].

Ioannidis, Nilah M. ;

Rothstein, Joseph H. ;

Pejaver, Vikas ;

Middha, Sumit ;

McDonnell, Shannon K. ;

Baheti, Saurabh ;

Musolf, Anthony ;

Li, Qing ;

Holzinger, Emily ;

Karyadi, Danielle ;

Cannon-Albright, Lisa A. ;

Teerlink, Craig C. ;

Stanford, Janet L. ;

Isaacs, William B. ;

Xu, Jianfeng ;

Cooney, Kathleen A. ;

Lange, Ethan M. ;

Schleutker, Johanna ;

Carpten, John D. ;

Powell, Isaac J. ;

Cussenot, Olivier ;

Cancel-Tassin, Geraldine ;

Giles, Graham G. ;

MacInnis, Robert J. ;

Maier, Christiane ;

Hsieh, Chih-Lin ;

Wiklund, Fredrik ;

Catalona, William J. ;

Foulkes, William D. ;

Mandal, Diptasri ;

Eeles, Rosalind A. ;

Kote-Jarai, Zsofia ;

Bustamante, Carlos D. ;

Schaid, Daniel J. ;

Hastie, Trevor ;

Ostrander, Elaine A. ;

Bailey-Wilson, Joan E. ;

Radivojac, Predrag ;

Thibodeau, Stephen N. ;

Whittemore, Alice S. ;

Sieh, Weiva .

AMERICAN JOURNAL OF HUMAN GENETICS, 2016, 99 (04) :877-885

[9] OCA5, a novel locus for non-syndromic oculocutaneous albinism, maps to chromosome 4q24 [J].

Kausar, T. ;

Bhatti, M. A. ;

Ali, M. ;

Shaikh, R. S. ;

Ahmed, Z. M. .

CLINICAL GENETICS, 2013, 84 (01) :91-93

[10] Whole exome sequencing identifies a novel compound heterozygous GFM1 variant underlying developmental delay, dystonia, polymicrogyria, and severe intellectual disability in a Pakhtun family [J].

Khan, Atta Ullah ;

Khan, Ibrar ;

Khan, Muhammad Ismail ;

Latif, Muhammad ;

Siddiqui, Muhammad Imran ;

Khan, Shafi Ullah ;

Htar, Thet Thet ;

Wahid, Ghazala ;

Ullah, Ikram ;

Bibi, Fehmida ;

Khan, Asifullah ;

Naseer, Muhammad Imran ;

Seo, Go Hun ;

Jelani, Musharraf .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2022, 188 (09) :2693-2700

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