Novel mutations in the USH2A gene in a family affected with Usher syndrome type 2

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 gene: c.5459T> C (p.M1820T) in exon 27, c.802G> A (p.G268R) in exon 5 and c.1 190T> 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. Key words: Usher syndromes/genetics; Usher syndromes/etiology; Genes; Mutation; Sequence analysis