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

The Annals of Otology, Rhinology, and Laryngology
Hideaki MotekiShin-Ichi Usami

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.

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Citations

Nov 3, 2016·Current Opinion in Pediatrics·Christina M Sloan-Heggen, Richard J H Smith
Aug 5, 2019·Purinergic Signalling·Jennie M E CederholmGary D Housley
Oct 23, 2019·Proceedings of the National Academy of Sciences of the United States of America·Benjamin GeorgeMufeng Li
Jun 2, 2020·Frontiers in Pharmacology·Leanne StokesElizabeth Allum
Apr 2, 2021·Human Molecular Genetics·Xiaoya ChenXue Zhong Liu
Sep 12, 2021·Proceedings of the National Academy of Sciences of the United States of America·Zhihui FongGerard P Sergeant

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Methods Mentioned

BETA
electrophoresis
PCR

Software Mentioned

GATK
Picard
Galaxy
Sciclone
BWA
PolyPhen2
SIFT
Mutation Taster
PhyloP
NGSRich

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