A Novel Frameshift Mutation of the USH2A Gene in a Korean Patient with Usher Syndrome Type II
A 34-year-old female was referred to our hospital because of bilateral hearing disturbance since childhood. She complained of a mild hearing difficulty but had not been wearing hearing aids. She had been also suffering from night blindness since adolescence and loss of visual field since age 17. Her visual deterioration had been progressive and she was almost blind at the time of presentation. She did not complain of vertigo. The family history was unremarkable. Physical examination revealed no obvious abnormalities of the external ear or tympanic membrane. For audiologic evaluation, pure tone audiogram (PTA), impedance audiogram, and auditory brainstem evoked response were performed. PTA showed bilateral down-sloping moderate sensorineural hearing loss (). The threshold of auditory brainstem response was 60 dB HL on both sides. Electronystagmography with a bithermal caloric test demonstrated non specific finding. Temporal bone computed tomography and magnetic resonance imaging showed no specific findings. On ophthalmologic examinations, the lens and the cornea were intact, but the fundoscopic examination revealed bony spicule pigmentation with attenuated retinal vessels in both eyes, the typical finding of RP (). The electroretinogram showed non-detectable waveforms in scotopic and photopic condition in both eyes. Taken together, she was clinically diagnosed as having USH2. The detailed clinical presentation of the patient was previously described by Boo et al. [].\nAfter obtaining written informed consent from the patient, genomic DNA was extracted from peripheral blood leukocytes. We performed polymerase chain reaction (PCR) and direct sequencing of all the 71 coding exons and their flanking intronic sequences of the USH2A using primer pairs designed by the authors. Direct sequencing was performed on the ABI Prism 3100 Genetic Analyzer with the BigDye Terminator Cycle Sequencing Ready Reaction kit (Applied Biosystems, Foster City, CA, USA). Sequence variations were analyzed with reference to the wild type sequence (GenBank accession No. NM_206933.1) using the Sequencher program (Gene Codes Corp., Ann Arbor, MI, USA). For the protein sequence, reference sequence NP_996816.2 was used. The sequence variation detected was described according to the recommendations by the Human Genome Variation Society, having the A of the ATG translation starting codon as +1 at the cDNA level and the corresponding methionine as +1 at the protein level.\nAs a result, we detected a heterozygous single nucleotide deletion in the exon 13 of the USH2A, which was expected to result in a frameshift leading to premature termination at the 787th codon (c.2310delA; p.Glu771LysfsX17) (). A review of the literature and the database revealed that this variation was a novel mutation. We also confirmed that the mutation was not observed in 200 control chromosomes.