Figure 1.
Pedigree and segregation of the mutation and fundus photograph of a patient from the family.
A. Kindred structure and segregation of ZNF664 S672G mutation in the high myopia family. Affected individuals are shown by solid squares (males) or circles (females). Normal individuals are identified by open symbols. Deceased individuals are indicated by a slash (/). M: 672G mutant allele of ZNF644; +: S672 normal allele of ZNF644. B. Fundus photograph of III:2 of the family, showing tigroid or tessellated features and conus pattern of retina. C. Normal fundus appearance of IV:5.
Table 1.
The clinical features of the high myopia family 951 with a ZNF644 gene mutation.
Figure 2.
The distribution of qualities of the sequencing reads for the two analyzed samples.
A. The sequencing quality of III:2. B. The sequencing quality of V:1. The X-axis represents the position along each sequence read. In this study we performed 80 bp sequencing, so the label of X-axis is from 0 to 80. The Y-axis is the Phred quality score of each base along sequence reads. The higher the score, the more accurate a base call. The quality scores of 20, 30 and 40 represent 99%, 99.9% and 99.99% accuracy of a base call. The intensity of the blue dot refers to the quantity of sequences with the same quality score. The darker the blue, the more bases/sequences at the dot. The quality scores of first 50 bp of most reads for both samples are higher than those of the last 30 bp, thus the darker blue dots accumulate around Q30 (Phred score of 30) from 0 to 30 bp along reads, while Q5 is observed between 60∼80 bp along reads. In order to get more accurate base calling, we filtered these low quality reads during the data analysis.
Table 2.
Summary statistics for exome sequencing for two individuals with high myopia.
Table 3.
Genetic variants identified through exome resequencing.
Figure 3.
Genomic structure of the exons encoding the open reading frame of ZNF644 and identified mutations.
Five out of six exons are translated (green), and exon 1 and portions of exon 2 and exon 6 are untranslated (red) in the ZNF644 gene (upper panel). Six different mutations in the ZNF644 gene and their sequencing traces are shown at the bottom of the figure (lower panel).
Figure 4.
Fundus photographs and optical coherence tomography (OCT) of high myopia patients from the sporadic cases.
A. The fundus of the patient JS047001 (Table 5) showing tigroid or tessellated features, conus, and CNV (choroid neovascularization). Optical Coherence Tomography (OCT) examination of this patient showed continuity of retinal pigment epithelial layer and broken photoreceptor layer (E). B. The fundus of the patient JS103001 (Table 5) showing tigroid or tessellated features, numerous areas of atrophy of the pigment epithelium, and choriocapillaries extending into the macular region and Fuchs spot. OCT examination of this patient showed discontinuity and irregular apophysis of the reflective pigment epithelial layer (F). C. The fundus of the patient JS104001 (Table 5) showing tigroid or tessellated features, numerous areas of atrophy of the pigment epithelium, and choriocapillaris. OCT examination of this patient showed foveal thinning and atrophies of the retinal neuroepithelial layer (G). D. Normal fundus photograph and OCT examination of a normal Control (H).
Table 4.
Characteristics of sporadic cases and controls in the study.
Table 5.
The clinical features of affected patients with a ZNF644 gene mutation in the 300 sporadic cases with high myopia.
Figure 5.
Expression of the ZNF644 gene in human tissues.
RT-PCR analyses of ZNF644 expression in the human liver, placenta, retina, and retinal pigment epithelium (RPE) with 255 bp of products. GAPDH was used as an internal control for cDNA quantification.