Yeungnam Univ J Med.  2021 Apr;38(2):160-164. 10.12701/yujm.2020.00339.

A new type of oculocutaneous albinism with a novel OCA2 mutation

• Lee SY
• Lee EJ
• Byun JC
• Jang KM
• Kim SY
• Hwang SK

• KMID: 2515192
• DOI: http://doi.org/10.12701/yujm.2020.00339

Abstract

Oculocutaneous albinism (OCA) is a group of rare genetically heterogeneous disorders, characterized by hypopigmentation of the eyes, skin, and hair, which result in ocular abnormalities and a risk of developing skin cancer. Currently, there is no ophthalmologic procedure or drug that prevents the clinical features of OCA. Here, we report a new type of OCA in two, unrelated Korean families with the same OCA2 mutation. Affected individuals in this study are different from those of previous reports in two aspects: an inheritance pattern and clinical presentation. All reported patients with OCA have shown an autosomal recessive inheritance pattern, while our patients showed an autosomal dominant inheritance pattern. Small amounts of pigment can be acquired with age in OCA, but there is no substantial variation from adolescence to adulthood in this regard. A case where the patient attained normal pigmentation levels has never been reported. However, our patients displayed completely normal pigmentation in their late twenties. Whole exome sequencing and in-silico analysis revealed a novel mutation, OCA2 c.2338G>A p.(G780S) (NM_000275) with a high likelihood of pathogenicity. Sanger sequencing of p.G780S identified the same mutation in the affected individuals, which was not found in the family members with normal phenotype. We hypothesize that OCA2 G780S not only acts as a pathogenic variant of OCA but also induces pigmentation by enhancing the melanogenesis gene expression of other modifier genes, such as SLC45A2 and TPC2. These findings may provide further understanding of melanin biosynthesis and new treatment methods for OCA.

Keyword

Autosomal dominant; Mutation; OCA2; Oculocutaneous albinism; Whole exome sequencing

Figure

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  Fig. 1. (A) General appearance of the affected son and the affected father of the first family at the time of visit. (B) The father of the patient also had oculocutaneous albinism when he was young. (C) Hypopigmented fundi of the affected son. (D) The pedigree shows autosomal dominant inheritance. (E) Chromatograms of family members showing the same OCA2 mutation in the affected individuals.

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  Fig. 2. (A) General appearance of the affected daughter at the time of visit. (B) General appearance of the affected daughter and her unaffected sister. (C) The affected daughter had pale white skin and blond hair when she was just born. (D) Hypopigmented fundi of the affected daughter. (E) The pedigree shows autosomal dominant inheritance. (F) Chromatograms of family members showing the same OCA2 mutation in the affected individuals.

Reference

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