Figure 1.
Family pedigrees, DNA chromatogram sequences, and sequence alignment of the identified mutational spots.
(A) Schematic representation of the relative linear location of all four MYO7A mutations identified in the present study in context of genome structure (upper) and protein structure (below). (B–D) Pedigrees of families USH01 (B), USH02 (C), and USH03 (D). Filled and empty symbols represent affected and unaffected individuals, respectively. Probands (USH01-III1, USH02-II1, and USH03-II1) are indicated by arrows. Consanguinity exits in family USH02. (E–H) DNA sequencing profiles for the four identified disease-causing mutations (left panel) and the corresponding wide type forms (right panel). Biallelic heterozygous c.1343+1G>A (E, MU1) and c.2837T>G (F, MU2, p.Met946Arg) mutations are identified as disease causing mutations for family USH01. Homozygous c.581_582del (G, MU3, p.Pro194Hisfs*13) and c.494C>T (H, MU4, p.Thr165Met) mutations are indicated as disease causative for family USH02 and USH03, respectively. (J) The arrows indicate that the Thr165 and Met946 residues are evolutionary highly conserved among multiple species.
Figure 2.
Pure tone audiometry results of the two patients in family USH01.
(A–B) Pure tone audiometry results of patient USH01-III1 show moderate bilateral hearing impairments. (C–D) Moderate to severe bilateral sensorineural hearing loss is revealed in patient USH01-III2.
Figure 3.
Fundus photographs of the included patients.
(A–B) Fundus photographs of the 24-year-old proband of family USH01 reveal attenuation of retinal vessels, pallor of optic disc, and pigmentary migration, indicating an atypical RP fundus. Macular region is not affected in both eyes. (C–D) Fundus appearance of patient USH01-III2 (22-year-old) is similar to that of patient USH01-III1. Attenuated retinal vessels and pale optic disc are observed. Macular region is also preserved. (E–F) Typical RP fundus is shown by patient USH03-II1, including bone spicule-like pigmentation, retinal vascular attenuation, pallor of optic disk, and chorioretinal atrophy. Macular degeneration is observed in this patient.
Table 1.
Clinical Manifestations of Patients Carrying MYO7A Mutations.
Figure 4.
Structural modeling of myosin-VIIa.
(A) Overview of the predicted structure of myosin-VIIa (3–769) covering the majority of the myosin head-like domain (1–729) and the first IQ motif (745–765). The ATP binding site (158–165) and the actin binding site (632–639) are included and are colored as red and green, respectively. The mutational spot identified in patient USH03-II:1 (Thr165) located in the ATP binding site is indicated in yellow. (B) A close view of the residue 165 highlighting the wide type amino acid threonine, the generated hydrogen bonds (in red), and their interacted amino acids, including Thr168, Lys169, Ser211, and Asp437. (C) Two previously indicated hydrogen bonds are eliminated due to the change of the wide type threonine into the mutant methionine.