Mutational Analysis of TYR, OCA2, and SLC45A2 Genes in Chinese Families with Oculocutaneous Albinism

Abstract

Background Oculocutaneous albinism (OCA) is a group of heterogeneous autosomal recessive genetic disorder of melanin synthesis results in hypopigmented hair, skin, and eyes. OCA type 1, OCA type 2, and OCA type 4, which are respectively caused by mutations in TYR , OCA2, and SLC45A2 have high morbidity rates in Asia. Methods TYR , OCA2, and SLC45A2 mutation analysis was carried out on 18 nonconsanguineous OCA patients and four fetuses were included for prenatal diagnose. Three genes of all individuals were amplified by polymerase chain reaction and examined by Sanger sequencing. The pathogenicity of the detected mutations were analyzed by Mutation Taster, PolyPhen 2, and SIFT software, and the conservation of the substituted amino acids were analyzed by MEGA software. Results Eleven TYR mutations, three OCA2 mutations, and two SLC45A2 mutations were identified in 14 OCA type 1 patients, two OCA type 2 patients, and two OCA type 4 patients. c.1021A>G, p.R341G in TYR , c.1096_1104del, p.V366*, and c.1079C>T, p.S360F in OCA2 were novel. One of the four fetuses carried compound heterozygous mutation of TYR and became spontaneous abortion, the other three carried no mutations and appeared normal at birth. Conclusion In this study, specific clinical characteristics of OCA patients were described. Three novel pathogenic mutations were identified which will enrich the mutation spectrum of OCA, and the prenatal genetic screening in fetus at risk of OCA can provide vital information for genetic counseling.

NGS-based targeted sequencing identified two novel variants in Southwestern Chinese families with oculocutaneous albinism

“…The insertion mutation c.559_560insCATTATTATGTGTCAAATTATCCCC, located on TYR exon1, has not been previously reported, following the American College of Medical Genetics and Genomics (ACMG) standards and guidelines for the interpretation and reporting of sequence variants, this variant was classified as “pathogenic” (Table 3 ). Missense mutations (64.3%, 9/14) in this study were the most frequent type in OCA1 patients, which is consistent with previous reports [ 20 , 21 ].…”

“…A total of 14 different TYR mutations were identified in this study: nine missense mutations (c.425A > T, c.1193A > G, c.880G > A, c.299G > T, c.1346A > G, c.1199G > T, c.230G > A, c.164G > A, and c.715C > T), two nonsense mutations (c.832C > T, c.346C > T), two insertion mutations (c.929dupC, c.559_560insCATTATTATGTGTCAAATTATCCCC), and one splicing mutation (c.820-3C > G). The insertion mutation, c.929dupC, located on TYR exon2, was the most frequent TYR mutation in our study, which is consistent with the data from Chinese and other East Asian countries, such as Korea and Japan [ 16 – 20 ]. The insertion mutation c.559_560insCATTATTATGTGTCAAATTATCCCC, located on TYR exon1, has not been previously reported, following the American College of Medical Genetics and Genomics (ACMG) standards and guidelines for the interpretation and reporting of sequence variants, this variant was classified as “pathogenic” (Table 3 ).…”

Database mining analysis revealed the role of the putative H+/sugar transporter solute carrier family 45 in skin cutaneous melanoma

“…Similar to tyrosinase, SLC45A2 may be regulated by the cAMP signaling pathway [ 5 ]. Because it is similar to the H+/ sucrose transporter in plants, the mechanism of its action may be to regulate the activity of tyrosinase through the transport of sucrose and H+, thus affecting the production of melanin [ 6 ]. SLC45A3 was mainly found to be clearly expressed in prostate tissues, both in normal prostate tissues and in tumor tissues [ 7 ].…”

Genetic Analysis of 28 Chinese Families With Tyrosinase-Positive Oculocutaneous Albinism

“…In addition, the gene product plays a role in regulating the pH of melanosomes ( Yuasa et al, 2007 ). Up to now, lots of OCA2 mutations have been reported and novel variants are still being discovered ( Maurano et al, 2012 ; Martinez-Garcia and Montoliu, 2013 ; Wang et al, 2016 ; Qiu et al, 2018 ; Lin et al, 2019 ; Luo et al, 2019 ; Yang et al, 2019 ; Zhong et al, 2019 ; Chuan et al, 2021 ; Xu et al, 2021 ). In recent years, multiple groups of researchers have conducted epidemiological surveys on Chinese albinism patients.…”

“…Although the proportions of each type are different, OCA1 is recognized as the main type of albinism, and exons 1 and 2 are mutation hotspots. The proportions of OCA2, OCA4, HPS1 and unknown mutations are behind ( Lin et al, 2019 ; Luo et al, 2019 ; Chuan et al, 2021 ; Xu et al, 2021 ).…”