Novel mutations in the USH2A gene in a family affected with Usher syndrome type 2 / 中华眼底病杂志

ABSTRACT

Objective To identify the pathogenic genes and mutations in a family with Usher syndrome type 2.Methods A three-generation family including 7 individuals was enrolled in this study.There were 2 male patients and 5 unaffected individuals.All participants was underwent related ophthalmologic examination,including best corrected visual acuity,slit-lamp,indirect ophthalmoscopy,electroretinogram (ERG),optical coherence tomography and visual field test.DNA was extracted from 3 ml peripheral venous blood of all participants.A total of 136 hereditary retinal disease target genes were screened and the DNA sequence was performed by Next-generation sequence analysis.Then the suspected mutations compared with databases to identify the suspected mutations,which should be verified with non-affected family members and 100 normal subjects by PCR and Sanger sequence.Results The sequence result showed that 2 patients,the proband and his brother,carried complex heterozygous mutations in the USH2A genec.5459T＞C (p.M1820T) in exon 27,c.802G ＞A (p.G268R) in exon 5 and c.1190T＞A (p.I397K) in exon 7.The c.5459T ＞ C and c.1190T ＞A mutations in USH2A have not been reported in the literature and database.Although their mother carried c.5459T＞C (p.M1820T) and c.802G＞A (p.G268R),and their father carried c.1190T＞A (p.I397K) heterozygous mutations,the parents did not present phenotype.These mutations were not detected in other normal family members.The result was supported by co-segregation analysis.Conclusion The heterozygous mutations c.5459T＞C (p.M1820T),c.1190T＞A (p.I397K) and c.802G＞A (p.G268R) in USH2A gene cause Usher syndrome in this family.