Aetiology of posterior uveitis in a tertiary centre in Finland

43.1 lV, left eye 7.32 lV, normal 93– 305 lV; which reflects rod response) and the maximal scotopic ERG (a waves: right eye 14.5 lV, left eye 12 lV, normal 155–356 lV; b waves: right eye 27.5 lV, left eye 31.9 lV, normal 290–654 lV; which reflects cone and rod response; Fig. 1E–G). After obtaining the approval of the Ethics Committee of Shenzhen Eye Hospital and informed consent from the patient and family members, we extracted genomic DNA from them and a screening of 381 pathogenic genes associated with retinal diseases in the patient was performed using targeted sequence capture array technique. Polymerase chain reaction and Sanger sequencing were used to confirm the screening results. We found that the proband (II2, Fig. 1) carries three point mutations in USH2A gene, including c.2187C>A (p.C729X), c.997T>C (p.S333P) and c.538T>C (p.S180P) (Fig. 2). Her father (I1, Fig. 1) carries the c.2187C>A (p.C729X) and c.997T>C(p.S333P) mutations in USH2A gene (Fig. 2), and her mother (I2, Fig. 1) carries the c.538T>C(p.S180P) mutation in USH2A gene (Fig. 2). One of her sisters was not found to carry any mutations in USH2A gene (Fig. 2). The high heterogeneity of clinical characteristics and genetic inheritance of USH makes it difficult to diagnose at molecular level by first-generation DNA sequencing. In this study, we screened the potential pathogenic gene mutations in the patient with USH by Targeted Genes Capture Sequencing. We found three mutations in USH2A gene, including c.2187C>A (p.C729X), c.997T>C (p.S333P) and c.538T>C (p.S180P). The genetic pattern of the family is autosomal recessive inheritance according to genetic analysis. Both the father and the mother have normal phenotypes. That means either c.2187C>A (p.C729X) and c.997T>C (p.S333P) (father) or c.538T>C (p.S180P) (mother) does not cause disease phenotypes. It has been reported that the missense mutation c. 538T > C (p. S180P) is associated with USH2 (Nakanishi et al. 2009). But it is recessive, not dominant. The single point mutation of c.538T>C (p. S180P) may not be sufficient to cause USH2. Currently, no other evidence shows that the missense mutation c.538T>C (p.S180P) is the cause of the USH. In addition, c.2187C>A (p. C729X) is a potential newly gene mutation due to a premature stop codon formed. The patient carries two point mutations from her father and one mutation from her mother, suggesting that it is a compound heterozygous mutation. Future studies will be performed to elucidate the pathophysiological mechanisms of retinal degeneration caused by the gene mutations. In this study, we found three new compound heterozygous mutations (c.2187C>A (p.C729X), c.997T>C (p.S333P) and c.538T>C (p.S180P)) in USH which were also a new pathogenic cause of USH2A. Our results indicate a distinctive mutation spectrum in this population which expand our knowledge of heterogenic phenotypes and genotypes through genetic diagnoses of the patient.