A novel mutation on OCA2 gene detection and preimplantationgenetic diagnosis for oculocutaneous albinism type 2 (OCA2)

Abstract

Oculocutaneous albinism (OCA) is a group of recessive genetic congenital disorders characterised by a disorder of melanin synthesis. OCA is currently classified into seven different types, of which OCA type 2 (OCA2 - OMIM 203200) ranks as the second most common type of albinism in the world and accounts for nearly 30% of albinism cases. Nowadays, there is currently no known way to treat OCA. Preimplantation genetic diagnosis (PGD) is the most effective method of disease prevention, which helps families carrying gene mutations to have healthy children. Objectives: To develop a procedure and conduct PGD for embryos of a family carrying the OCA2 mutation causing OCA2. Materials and methods: Research subjects are blood samples of four members of an OCA family, including father, mother, and two daughters; and 6 embryo biopsies on day 5 of this parents. Next-generation sequencing (NGS) was carried out on family members participating in the study. Based on the identified mutation results, primers for PCR amplification of the segments spanning the detected mutation were designed. Then, Sanger sequencing method is combined with linkage genetic analysis to detect pathogenic mutations on embryo biopsies after whole-genome amplification (WGA). Results: A novel mutation NM_000275.3:c.2323G>A (NP_000266.2: p.Gly775Ser) was detected on exon 22 of the OCA2 gene. The outcomes of PGD for 6 embryos of a family carrying the OCA2 mutant gene causing OCA2 were 3 affected embryos, 2 normal embryos, and 1 carriers.