Figure 1.
Electropherograms of the 6 likely pathogenic EYS mutations.
Partial sequence of the EYS gene showing the normal control sequences (A-1 through F-1), heterozygous mutation sequences (A-2 through F-2), and homozygous mutation sequences (A-3 and C-3). Deduced amino acids are indicated under the sequence trace. The mutation location is indicated either by an arrow (for a nucleotide change) or a horizontal line (to show 2 nucleotides between which the insertion occurred). (A) c.4957_4958insA; p.S1653KfsX2 (Exon 26), (B) c.6557G>A; p.G2186E (Exon 32), (C) c.8868C>A; p.Y2956X (Exon 44), (D) c.8351T>G; p.L2784R (Exon 44), (E) c.7793G>A; p.G2598D (Exon 40), (F) c.2522_2523insA; p.Y841X (Exon 16).
Table 1.
Mutation spectrum of the EYS gene in Japanese families.
Table 2.
Summary of the very likely and possible pathogenic mutations identified in 100 Japanese arRP patients.
Figure 2.
Pedigrees of the families that was available for mutation analysis.
Below the individuals, genotypes are presented for either p.S1653KfsX2 (M1), p.L2784R (M2), p.Y2956X (M3), p.Y841X (M4), or p.G2186E (M5) detected to segregate with RP. M1/M1 represents homozygous mutation. M1/+ indicates heterozygous carriers, +/+ indicates individuals carrying 2 wild-type alleles, whereas M1/M2 represents individuals presenting both mutations as compound heterozygous. Square boxes indicate men, circles denote women, and affected individuals are pointed out by a black symbol. Slashed symbols indicate deceased individuals. The probands are indicated with an arrow. NA denotes unavailable DNA samples.
Figure 3.
Predicted domain structure and distribution of identified EYS mutations.
SMART (http://smart.embl-heidelberg.de/) and Pfam (http://pfam.sanger.ac.uk/) were used to search protein functional domains. A coiled-coil domain identified by Barragán et al. (2010) between the EGF-like domain and laminin G domain was also indicated. Novel very likely pathogenic mutations, novel possible pathogenic mutations, and a previously described mutation are shown in bold, normal, and italic type, respectively. Six out of 9 missense mutations were found in the EGF or laminin G domains. Furthermore, 7 were located in the latter half of the protein between the putative coiled-coil region and C-terminus.
Table 3.
Summary of the possible non-pathogenic sequence alterations in the EYS gene identified in this study.