Figure 1.
Pedigree of Chinese Family 7162 with Recessive USH1 and segregation of the mutations in MYO7A.
The proband is indicated by an arrow. Subject I:1, I:2, II:1, II:2, II:3 and II:4 were tested by NGS. gDNA from II:5 is not available.
Figure 2.
Audiogram showed bilateral profound sensorineural hearing loss of affected subjects II:4 and normal hearing of subject II:3 (red, right ear; blue, left ear).
Figure 3.
Composite image of the fundus photographs of individuals from family 7162.
A: The appearance of the fundus in one patient (II:4) with RP at 54 year old shows typical retinal degeneration with obvious waxy pallor of the optic discs, attenuation of the retinal vessels, irregular pigment clumps in the retina. B: Fundus photographs of patient II:1 without RP at 62 years old shows bright optic disc where blood vessels converge.
Figure 4.
Domain structure, conservation analysis and mutational analysis of MYO7A in family 7162.
A: Domain structure of myosin VIIa showing the nonsense mutation introduces a premature stop codon which is predicted to truncate the protein within the N-terminal motor domain. B: Protein alignment showing conservation of residues myosin VIIaG25 and C154 across nine species. Two mutations both occurred at evolutionarily conserved amino acids (in red box). C: DNA sequencing profile showing the c.73G>A and c.462C>A mutations in MYO7A. Both variants co-segregated with the clinical phenotype and c.462C>A were absent in 219 ethnicity-matched controls.
Figure 5.
Structure of wild-type and mutant myosin VIIa.
A: G25 in the wild-type protein has no side chain to interact with the His9 and Met59. B: The distance (dotted lines) between the long side chain of R25 and the residues H9 and M59 in the mutant protein were less than 3.5Å, which is shorter enough to form new hydrogen bonds (Created by SWISS-MODEL and shown with PY-MOL).