Genetic Analysis of Albinism Caused by Compound Heterozygous Mutations of the OCA2 Gene in a Chinese Family

Overview

Journal Hereditas

Specialty Genetics

Date 2024 Feb 5

PMID 38317267

Authors

Yanan Wang

Yujie Chang

Mingya Gao

Weiwei Zang

Xiaofei Liu

Affiliations

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Abstract

Background: Oculocutaneous albinism (OCA) is a group of rare genetic disorders characterized by a reduced or complete lack of melanin in the skin, hair, and eyes. Patients present with colorless retina, pale pink iris, and pupil, and fear of light. The skin, eyebrows, hair, and other body hair are white or yellowish-white. These conditions are caused by mutations in specific genes necessary for the production of melanin. OCA is divided into eight clinical types (OCA1-8), each with different clinical phenotypes and potential genetic factors. This study aimed to identify the genetic causes of non-syndromic OCA in a Chinese Han family.

Methods: We performed a comprehensive clinical examination of family members, screened for mutation loci using whole exome sequencing (WES) technology, and predicted mutations using In silico tools.

Results: The patient's clinical manifestations were white skin, yellow hair, a few freckles on the cheeks and bridge of the nose, decreased vision, blue iris, poorly defined optic disk borders, pigmentation of the fundus being insufficient, and significant vascular exposure. The WES test results indicate that the patient has compound heterozygous mutations in the OCA2 gene (c.1258G > A (p.G420R), c.1441G > A (p.A481T), and c.2267-2 A > C), respectively, originating from her parents. Among them, c.1258G > A (p.G420R) is a de novo mutation with pathogenic. Our analysis suggests that compound heterozygous mutations in the OCA2 gene are the primary cause of the disease in this patient.

Conclusions: The widespread application of next-generation sequencing technologies such as WES in clinical practice can effectively replace conventional detection methods and assist in the diagnosis of clinical diseases more quickly and accurately. The newly discovered c.1258G > A (p.G420R) mutation can update and expand the gene mutation spectrum of OCA2-type albinism.

Citing Articles

Genotypic and phenotypic analysis of an oculocutaneous albinism patient: a case report and review of the literature.

Ma Q, Wang W J Med Case Rep. 2024; 18(1):624.

PMID: 39695711 PMC: 11654439. DOI: 10.1186/s13256-024-04991-5.

References

Sviderskaya E, Bennett D, Ho L, Bailin T, Lee S, Spritz R . Complementation of hypopigmentation in p-mutant (pink-eyed dilution) mouse melanocytes by normal human P cDNA, and defective complementation by OCA2 mutant sequences. J Invest Dermatol. 1997; 108(1):30-4. DOI: 10.1111/1523-1747.ep12285621. View

Ullah M . Clinical and Mutation Spectrum of Autosomal Recessive Non-Syndromic Oculocutaneous Albinism (nsOCA) in Pakistan: A Review. Genes (Basel). 2022; 13(6). PMC: 9222488. DOI: 10.3390/genes13061072. View

Bellono N, Escobar I, Lefkovith A, Marks M, Oancea E . An intracellular anion channel critical for pigmentation. Elife. 2014; 3:e04543. PMC: 4270065. DOI: 10.7554/eLife.04543. View

Norman C, OGorman L, Gibson J, Pengelly R, Baralle D, Ratnayaka J . Identification of a functionally significant tri-allelic genotype in the Tyrosinase gene (TYR) causing hypomorphic oculocutaneous albinism (OCA1B). Sci Rep. 2017; 7(1):4415. PMC: 5493628. DOI: 10.1038/s41598-017-04401-5. View

Singh R, Bhardwaj V, Purohit R . Identification of a novel binding mechanism of Quinoline based molecules with lactate dehydrogenase of . J Biomol Struct Dyn. 2020; 39(1):348-356. DOI: 10.1080/07391102.2020.1711809. View

Suzuki T, Tomita Y . Recent advances in genetic analyses of oculocutaneous albinism types 2 and 4. J Dermatol Sci. 2008; 51(1):1-9. DOI: 10.1016/j.jdermsci.2007.12.008. View

Wei A, Yang X, Lian S, Li W . Implementation of an optimized strategy for genetic testing of the Chinese patients with oculocutaneous albinism. J Dermatol Sci. 2011; 62(2):124-7. DOI: 10.1016/j.jdermsci.2011.02.009. View

Kumar A, Rajendran V, Sethumadhavan R, Purohit R . In silico prediction of a disease-associated STIL mutant and its affect on the recruitment of centromere protein J (CENPJ). FEBS Open Bio. 2013; 2:285-93. PMC: 3678130. DOI: 10.1016/j.fob.2012.09.003. View

Mukinayi B, Mpoyi Kalenda J, Kalombo Kalenda D, Disashi Tumba G, Gulbis B . Co-occurrence of sickle cell disease and oculocutaneous albinism in a Congolese patient: a case report. J Med Case Rep. 2021; 15(1):628. PMC: 8686233. DOI: 10.1186/s13256-021-03214-5. View

10.

Qiu B, Ma T, Peng C, Zheng X, Yang J . Identification of Five Novel Variants in Chinese Oculocutaneous Albinism by Targeted Next-Generation Sequencing. Genet Test Mol Biomarkers. 2018; 22(4):252-258. DOI: 10.1089/gtmb.2017.0211. View

11.

Wei A, Wang Y, Long Y, Wang Y, Guo X, Zhou Z . A comprehensive analysis reveals mutational spectra and common alleles in Chinese patients with oculocutaneous albinism. J Invest Dermatol. 2009; 130(3):716-24. DOI: 10.1038/jid.2009.339. View

12.

Wei A, Zhang T, Yuan Y, Qi Z, Bai D, Zhang Y . Spectrum Analysis of Albinism Genes in a Large Cohort of Chinese Index Patients. J Invest Dermatol. 2021; 142(6):1752-1755.e3. DOI: 10.1016/j.jid.2021.11.014. View

13.

Power B, Ferreira C, Chen D, Zein W, OBrien K, Introne W . Hermansky-Pudlak syndrome and oculocutaneous albinism in Chinese children with pigmentation defects and easy bruising. Orphanet J Rare Dis. 2019; 14(1):52. PMC: 6385472. DOI: 10.1186/s13023-019-1023-7. View

14.

Yousaf S, Sethna S, Chaudhary M, Shaikh R, Riazuddin S, Ahmed Z . Molecular characterization of SLC24A5 variants and evaluation of Nitisinone treatment efficacy in a zebrafish model of OCA6. Pigment Cell Melanoma Res. 2020; 33(4):556-565. PMC: 7269830. DOI: 10.1111/pcmr.12879. View

15.

Gronskov K, Ek J, Brondum-Nielsen K . Oculocutaneous albinism. Orphanet J Rare Dis. 2007; 2:43. PMC: 2211462. DOI: 10.1186/1750-1172-2-43. View

16.

Dolinska M, Anderson D, Sergeev Y . In vitro characterization of the intramelanosomal domain of human recombinant TYRP1 and its oculocutaneous albinism type 3-related mutant variants. Protein Sci. 2022; 32(1):e4518. PMC: 9793978. DOI: 10.1002/pro.4518. View

17.

Fernandez A, Hayashi M, Garrido G, Montero A, Guardia A, Suzuki T . Genetics of non-syndromic and syndromic oculocutaneous albinism in human and mouse. Pigment Cell Melanoma Res. 2021; 34(4):786-799. DOI: 10.1111/pcmr.12982. View

18.

Liu S, Kuht H, Moon E, Maconachie G, Thomas M . Current and emerging treatments for albinism. Surv Ophthalmol. 2020; 66(2):362-377. DOI: 10.1016/j.survophthal.2020.10.007. View

19.

Kamaraj B, Purohit R . Computational screening of disease-associated mutations in OCA2 gene. Cell Biochem Biophys. 2013; 68(1):97-109. DOI: 10.1007/s12013-013-9697-2. View

20.

Kausar T, Bhatti M, Ali M, Shaikh R, Ahmed Z . OCA5, a novel locus for non-syndromic oculocutaneous albinism, maps to chromosome 4q24. Clin Genet. 2012; 84(1):91-3. DOI: 10.1111/cge.12019. View