title: Hearing loss caused by a P2RX2 mutation identified in a MELAS family with a coexisting mitochondrial 3243AG mutation.
abstract: OBJECTIVE
  We present a family with a mitochondrial DNA 3243A>G mutation resulting in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), of which some members have hearing loss in which a novel mutation in the P2RX2 gene was identified.
  
  
  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 performed to identify the genetic causes of hearing loss.
  
  
  RESULTS
  A novel mutation in the P2RX2 gene that corresponded to c.601G>A (p.Asp201Tyr) was identified. Two patients carried the mutation and had severe sensorineural hearing loss, while other members with MELAS (who did not carry the P2RX2 mutation) had normal hearing.
  
  
  CONCLUSIONS
  This is the first case report of a diagnosis of hearing loss caused by P2RX2 mutation in patients with MELAS. A potential explanation is that a decrease in adenosine triphosphate (ATP) production due to MELAS with a mitochondrial 3243A>G mutation might suppress activation of P2X2 receptors. We also suggest that hearing loss caused by the P2RX2 mutation might be influenced by the decrease in ATP production due to MELAS.
authors: 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, Iowa, USA Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto, Japan.
authors: Hideaki
authors: H
authors: Moteki
authors: Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
authors: Hela
authors: H
authors: Azaiez
authors: Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
authors: Kevin T
authors: KT
authors: Booth
authors: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors: Mitsuru
authors: M
authors: Hattori
authors: Division of Diabetes, Endocrinology and Metabolism: Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors: Ai
authors: A
authors: Sato
authors: Division of Diabetes, Endocrinology and Metabolism: Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors: Yoshihiko
authors: Y
authors: Sato
authors: Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
authors: Mitsuo
authors: M
authors: Motobayashi
authors: Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
authors: Christina M
authors: CM
authors: Sloan
authors: Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
authors: Diana L
authors: DL
authors: Kolbe
authors: Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
authors: A Eliot
authors: AE
authors: Shearer
authors: Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
authors: Richard J H
authors: RJ
authors: Smith
authors: 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.
authors: Shin-Ichi
authors: S
authors: Usami
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D003638:Deafness / Q000235:genetics; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D010375:Pedigree; D058476:Receptors, Purinergic P2X2 / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: C546401:P2RX2 protein, human; D058476:Receptors, Purinergic P2X2; D000255:Adenosine Triphosphate
keywords: MELAS; P2X2; genetics; hearing loss; massively parallel sequencing