Novel and recurrent MYO7A mutations in Usher syndrome type 1 and type 2.
Usher syndrome (USH) is a group of disorders manifested as retinitis pigmentosa and bilateral sensorineural hearing loss, with or without vestibular dysfunction. Here, we recruited three Chinese families affected with autosomal recessive USH for detailed clinical evaluations and for mutation screening in the genes associated with inherited retinal diseases. Using targeted next-generation sequencing (NGS) approach, three new alleles and one known mutation in MYO7A gene were identified in the three families. In two families with USH type 1, novel homozygous frameshift variant p.Pro194Hisfs*13 and recurrent missense variant p.Thr165Met were demonstrated as the causative mutations respectively. Crystal structural analysis denoted that p.Thr165Met would very likely change the tertiary structure of the protein encoded by MYO7A. In another family affected with USH type 2, novel biallelic mutations in MYO7A, c.[1343+1G>A];[2837T>G] or p.[?];[Met946Arg], were identified with clinical significance. Because MYO7A, to our knowledge, has rarely been correlated with USH type 2, our findings therefore reveal distinguished clinical phenotypes associated with MYO7A. We also conclude that targeted NGS is an effective approach for genetic diagnosis for USH, which can further provide better understanding of genotype-phenotype relationship of the disease.
Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
Weining
W
Rong
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China; Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Xue
X
Chen
Tianjin Medical University, Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, China.
Kanxing
K
Zhao
Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
Yani
Y
Liu
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China.
Xiaoxing
X
Liu
Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
Shaoping
S
Ha
Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
Wenzhou
W
Liu
Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaoli
X
Kang
Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
Xunlun
X
Sheng
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat Sen University, Guangzhou, China.
Chen
C
Zhao
D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D005654:Fundus Oculi; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020125:Mutation, Missense; D000081412:Myosin VIIa; D009218:Myosins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D052245:Usher Syndromes / Q000235:genetics*; D055815:Young Adult
C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009218:Myosins