Novel compound heterozygous mutations in OCA2 gene were identified in a Chinese family with oculocutaneous albinism

• Published in: Molecular genetics & genomic medicine 2024-01, Vol.12 (1), p.e2297-n/a
• Main Authors: Jiang, Beilei, Zhang, Hua, Kan, Yuling, Gao, Xueping, Du, Zhaoli, Liu, Quan
• Format: Article
• Language: English
• Subjects: African Americans; Albinism; Amniotic fluid; Bioinformatics; Exons; Fetuses; Gene deletion; Gene sequencing; Genetic counseling; Genetic testing; Genetics; Genomes; Helices; Heterogeneity; Leucine; Mutation; OCA2; oculocutaneous albinism; Proteins; whole‐exome sequencing
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.2297

Background Oculocutaneous albinism (OCA) is a group of rare autosomal recessive disorders characterized by clinical genetic heterogeneity. OCA type II (OMIM: 203200) is the most common subtype among African and African Americans, primarily caused by pathogenic variants in the OCA2 (HGNC ID: 8101) gene. In this study, we presented a Chinese family with OCA and reported two novel variants in the OCA2 gene. Methods Whole‐exome sequencing (WES) was performed to identify pathogenic variants in the proband. The candidate variants were subsequently validated using Sanger sequencing and QPCR assay. Additionally, bioinformatics analyses were employed to predict the deleteriousness and conservation of the identified mutations. Results In the 16‐year‐old male proband, two novel compound heterozygous OCA2 variants, NM_000275.3: c.1640T>G (NP_000266.2: p.L547R) and an exons 10‐19 deletion variant, were identified. Meanwhile, a reported heterozygous variant c.1441G>A/p.A481T (NM_000275.3, NP_000266.2) in the OCA2 gene was also found in the proband. Sanger sequencing confirmed that the two variants c.1441G>A/p.A481T and c.1640T>G/p.L547R were inherited from his father. Moreover, qPCR assay revealed that the exons 10‐19 deletion was inherited from the mother, his sister also carried this variant. Fortunately, the variant was not detected in the amniotic fluid of the proband's sister. Multiple online bioinformatics tools predicted the variant c.1640T>G to be damaging, leading to the replacement of a highly conserved leucine with an arginine. The gross exon 10‐19 deletion in the OCA2 gene resulted in a truncated, non‐functional protein losing the 3–9 transmembrane α‐helices domains. According to the American College of Medical Genetics and Genomics classification, these three variants in the OCA2 gene were evaluated as likely pathogenic. Conclusion This study has identified two novel compound variants in the OCA2 gene and a previously reported variant in a Chinese family with OCA. By expanding the mutation spectrum of the OCA2 gene, our findings contribute to a better understanding of the genetic basis of OCA. The present study identified two novel compound variants in OCA2 gene in a Chinese family with oculocutaneous albinism. These findings expand the mutation spectrum of OCA2 gene.