A Genetic Study Of TYR Gene In Seventeen Patients With Oculocutaneous Albinism

Objective: To describe mutations of TYR gene in Seventeen patients with non-syndromic OCA and explore the pathogenic genes and sites and pathogenic mechanisms.Methods: Routine screenings and complete ophthalmological examinations were performed on all participants after obtained signed informed consent.Total genomic DNA was isolated from peripheral blood.We screened the whole exons and their flanking regions of TYR gene by Sanger sequencing and predicted the pathogenicity of variants by in Silico analysis.Results: Seventeen patients with non-syndromic OCA were enrolled from 8 provinces of China and are not consanguineous except for Patient 4000301.Total genomic DNA was isolated from peripheral blood.We screened the whole exons and their flanking regions of TYR gene by Sanger sequencing and predicted the pathogenicity of variants by in Silico analysis.12 TYR mutations were identified in ten patients,respectively.Two patients carried homozygous mutations and eight patients carried compound heterozygous mutations.Patient 4000101 was a compound heterozygote of mutations c.1A>G（p.M1?）and c.896G>A（p.R299H）in TYR gene.Patient 4000201 was compound heterozygote of mutations c.1198T>G（p.W400G）and c.896G>A（p.R299H）.Patient 4000301 from a consanguineous family was homozygote of the mutation c.929₉30ins C（p.R311Kfs*7）.Patient 4000701 was compound heterozygous for c.929₉30ins C（p.R311Kfs*7）and c.896G>A（p.R299H）.Patient 4000801 was found to have a homozygous genotype of c.819G>T（p.Q273H）.Patient 4000901 was compound heterozygote of mutations c.758G>A（p.G253E）and c.896G>A（p.R299H）.Patient 4001101 was compound heterozygote of mutations c.231₂32ins GGG（p.R77_E78ins G）and c.230G>A（p.R77Q）,and c.230G>A was confirmed in his normal family member（Figure S1）.Patient 4001301 carried mutations c.346C>T（p.R116*）and c.832C>T（p.R278*）,and patient 4001501 carried mutations c.896G>A（p.R299H）and c.70T>C（p.C24R）,and patient 4001701 carried the mutation c.231-232 ins GGG（p.R77_E78ins G）and a splicing mutation c.1037-7T>A.Among 12 TYR mutations,two missense mutations c.1198T>G（p.W400G）and c.819G>T（p.Q273H）were novel.Conclusion: mutation analysis of TYR gene in 17 patients with nonsyndromic OCA shows that 12 different mutations of TYR may be the cause of OCA in ten patients.Among these mutations,two novel mutations c.1198T>G（p.W400G）and c.819G>T（p.Q273H）expand the mutation spectrum of TYR in OCA,which may further aid the prenatal examination and genetic diagnosis of OCA and offer a better look into the molecular mechanism of OCA1.