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, 32 (5), 672-686

Comprehensive Analysis of Spectral Distribution of a Large Cohort of Chinese Patients With Non-Syndromic Oculocutaneous Albinism Facilitates Genetic Diagnosis

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Comprehensive Analysis of Spectral Distribution of a Large Cohort of Chinese Patients With Non-Syndromic Oculocutaneous Albinism Facilitates Genetic Diagnosis

Zilin Zhong et al. Pigment Cell Melanoma Res.

Abstract

Non-syndromic oculocutaneous albinism (nsOCA) is a group of genetically heterogeneous autosomal recessive disorders with complete lack or decrease pigmentation in skin, hair, and eyes. TYR, OCA2, TYRP1, SLC45A2, SLC24A5, and LRMDA were reported to cause OCA1-4 and OCA6-7, respectively. By sequencing all the known nsOCA genes in 114 unrelated Chinese nsOCA patients combined with In silico analyses, splicing assay, and classification of variants according to the standards and guidelines of American College of Medical Genetics and Genomics, we detected seventy-one different OCA-causing variants separately in TYR, OCA2, SLC45A2, and SLC24A5, including thirty-one novel variants (13 in TYR, 11 in OCA2, and 7 in SLC45A2). This study shows that OCA1 is the most common (75/114) and OCA2 ranks the second most common (16/114) in Chinese. 99 patients of our cohort were caused by variants of all the known nsOCA genes. Cutaneous phenotypes of OCA1, OCA2, and OCA4 patients were shown in this study. The second OCA6 case in China was identified here. These data expand the spectrum of OCA variants as well phenotype and facilitate clinical implement of Chinese OCA patients.

Keywords: genes; oculocutaneous albinism; phenotype; variants.

Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Sequence chromatograms of novel variants in TYR, OCA2, SLC45A2, and SLC24A5
Figure 2
Figure 2
Splicing assay shows variant‐induced change in OCA2 or SLC45A2 splicing. Gel electrophoresis of RT‐PCR products for all tested constructs. Lane 1: 100bp marker, splicing assay is based on comparative assay about the splicing pattern of genomic fragment of wild‐type (WT) and mutant (MUT), respectively. Lane 2 and lane 3 as a group are to evaluate the change in splicing which the variant OCA2_c.808‐3C>G brought about. Lane 4 and lane 5 are for OCA2_c.2140‐2A>G; lane 6 and lane 7 are for SLC45A2_c.1032+1G>T; lane 8 and lane 9 are for OCA2_c.646+3A>G. The differences in the size and composition of band(s) between WT and MUT demonstrate the variant‐induced aberrant in mRNA level. (a) In vitro splicing assay in HeLa cell line. (b) In vitro splicing assay in ARPE‐19 cell line
Figure 3
Figure 3
Spectral distribution of variants of all known OCA genes in Chinese nsOCA patients. (a) The prevalence of OCA types in our cohort. (b) Distribution of variants in exons of known OCA genes identified in this study. (c) Distribution of variants in exon 1 of TYR. (d) Distribution of variants in exon 2 of TYR
Figure 4
Figure 4
Phenotypes in skin and hairs of patients with different types of nsOCA

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