Hearing loss caused by a P2RX2 mutation identified in a MELAS family with a coexisting mitochondrial 3243AG mutation

Hideaki Moteki; Hela Azaiez; Kevin T Booth; Diana L Kolbe; Mitsuru Hattori; Richard J H Smith; Ai Sato; Yoshihiko Sato; Mitsuo Motobayashi; Christina M Sloan; A Eliot Shearer; Shin-Ichi Usami

doi:10.1177/0003489415575045

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Hearing loss caused by a P2RX2 mutation identified in a MELAS family with a coexisting mitochondrial 3243AG mutation

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Hearing loss caused by a P2RX2 mutation identified in a MELAS family with a coexisting mitochondrial 3243AG mutation

Hideaki Moteki, Hela Azaiez, Kevin T Booth, Diana L Kolbe, Mitsuru Hattori, Richard J H Smith, Ai Sato, Yoshihiko Sato, Mitsuo Motobayashi, Christina M Sloan, …

Annals of otology, rhinology & laryngology, Vol.124 Suppl 1(1_suppl), pp.177S-183S

05/2015

DOI: 10.1177/0003489415575045

PMCID: PMC4441871

PMID: 25788561

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Abstract

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. 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. 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. 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.

Receptors, Purinergic P2X2 - genetics

Deafness - genetics

Humans

Middle Aged

Hearing Loss, Sensorineural - genetics

MELAS Syndrome - metabolism

MELAS Syndrome - genetics

Mitochondria - genetics

Pedigree

Adenosine Triphosphate - metabolism

Female

High-Throughput Nucleotide Sequencing

Sequence Analysis, DNA - methods

Details

Title: Subtitle: Hearing loss caused by a P2RX2 mutation identified in a MELAS family with a coexisting mitochondrial 3243AG mutation
Creators: Hideaki Moteki - 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
Hela Azaiez - Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Kevin T Booth - Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Diana L Kolbe - Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Mitsuru Hattori - Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan
Richard J H Smith - Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Ai Sato - Division of Diabetes, Endocrinology and Metabolism: Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan
Yoshihiko Sato - Division of Diabetes, Endocrinology and Metabolism: Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan
Mitsuo Motobayashi - Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan
Christina M Sloan - Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
A Eliot Shearer - Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Shin-Ichi Usami - 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
Resource Type: Journal article
Publication Details: Annals of otology, rhinology & laryngology, Vol.124 Suppl 1(1_suppl), pp.177S-183S
DOI: 10.1177/0003489415575045
PMID: 25788561
PMCID: PMC4441871
NLM abbreviation: Ann Otol Rhinol Laryngol
ISSN: 0003-4894
eISSN: 1943-572X
Publisher: United States
Grant note: R01 DC003544 / NIDCD NIH HHS R01 DC012049 / NIDCD NIH HHS R01 DC002842 / NIDCD NIH HHS T32 GM007337 / NIGMS NIH HHS
Language: English
Date published: 05/2015
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine; Iowa Institute of Human Genetics
Record Identifier: 9984007160102771

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