USH2 caused by GPR98 mutation diagnosed by massively parallel sequencing in advance of the occurrence of visual symptoms.
OBJECTIVE
We present 2 patients who were identified with mutations in the GPR98 gene that causes Usher syndrome type 2 (USH2).


METHODS
One hundred ninety-four (194) Japanese subjects from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were used to identify the genetic causes of hearing loss.


RESULTS
We identified causative mutations in the GPR98 gene in 1 family (2 siblings). The patients had moderate sloping hearing loss, and no progression was observed over a period of 10 years. Fundus examinations were normal. However, electroretinograms revealed impaired responses in both patients.


CONCLUSIONS
Early diagnosis of Usher syndrome has many advantages for patients and their families. This study supports the use of comprehensive genetic diagnosis for Usher syndrome, especially prior to the onset of visual symptoms, to provide the highest chance of diagnostic success in early life stages.
Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, IA, USA Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto, Japan.
Hideaki
H
Moteki
Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
Hidekane
H
Yoshimura
Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
Hela
H
Azaiez
Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
Kevin T
KT
Booth
Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
A Eliot
AE
Shearer
Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
Christina M
CM
Sloan
Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
Diana L
DL
Kolbe
Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto, Japan.
Toshinori
T
Murata
Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
Richard J H
RJ
Smith
Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto, Japan usami@shinshu-u.ac.jp.
Shin-Ichi
S
Usami
D000293:Adolescent; D044466:Asian People / Q000235:genetics; D004596:Electroretinography; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D052245:Usher Syndromes / Q000235:genetics*
C417525:ADGRV1 protein, human; D043562:Receptors, G-Protein-Coupled
GPR98; Usher syndrome; genetics; hearing loss; massively parallel sequencing