A C-terminal nonsense mutation links PTPRQ with autosomal-dominant hearing loss, DFNA73.

A C-terminal nonsense mutation links PTPRQ with autosomal-dominant hearing loss, DFNA73.

Genet Med. 2017 Oct 12;:

Authors: Eisenberger T, Di Donato N, Decker C, Delle Vedove A, Neuhaus C, Nürnberg G, Toliat M, Nürnberg P, Mürbe D, Bolz HJ

Abstract
PurposeHearing loss is genetically extremely heterogeneous, making it suitable for next-generation sequencing (NGS). We identified a four-generation family with nonsyndromic mild to severe hearing loss of the mid- to high frequencies and onset from early childhood to second decade in seven members.MethodsNGS of 66 deafness genes, Sanger sequencing, genome-wide linkage analysis, whole-exome sequencing (WES), semiquantitative reverse-transcriptase polymerase chain reaction.ResultsWe identified a heterozygous nonsense mutation, c.6881G>A (p.Trp2294*), in the last coding exon of PTPRQ. PTPRQ has been linked with recessive (DFNB84A), but not dominant deafness. NGS and Sanger sequencing of all exons (including alternatively spliced 5' and N-scan-predicted exons of a putative "extended" transcript) did not identify a second mutation. The highest logarithm of the odds score was in the PTPRQ-containing region on chromosome 12, and p.Trp2294* cosegregated with hearing loss. WES did not identify other cosegregating candidate variants from the mapped region. PTPRQ expression in patient fibroblasts indicated that the mutant allele escapes nonsense-mediated decay (NMD).ConclusionKnown PTPRQ mutations are recessive and do not affect the C-terminal exon. In contrast to recessive loss-of-function mutations, c.6881G>A transcripts may escape NMD. PTPRQTrp2294* protein would lack only six terminal residues and could exert a dominant-negative effect, a possible explanation for allelic deafness, DFNA73, clinically and genetically distinct from DFNB84A.GENETICS in MEDICINE advance online publication, 12 October 2017; doi:10.1038/gim.2017.155.

PMID: 29309402 [PubMed - as supplied by publisher]

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Identification of Novel PTPRQ and MYO1A Mutations in An Iranian Pedigree with Autosomal Recessive Hearing Loss.

Related Articles

Identification of Novel PTPRQ and MYO1A Mutations in An Iranian Pedigree with Autosomal Recessive Hearing Loss.

Cell J. 2018 Apr;20(1):127-131

Authors: Talebi F, Ghanbari Mardasi F, Mohammadi Asl J, Tizno S, Najafvand Zadeh M

Abstract
Autosomal recessive non-syndromic hearing loss (ARNSHL) is defined as a genetically heterogeneous disorder. The aim of the present study was to screen for pathogenic variants in an Iranian pedigree with ARNSHL. Next-generation targeted sequencing of 127 deafness genes in the proband detected two novel variants, a homozygous missense variant in PTPRQ (c.2599 T>C, p.Ser867Pro and a heterozygous missense variant in MYO1A (c.2804 T>C, p.Ile935Thr), both of which were absent in unaffected sibs and two hundred unaffected controls. Our results suggest that the homozygous PTPRQ variant maybe the pathogenic variant for ARNSHL due to the recessive nature of the disorder. Nevertheless, the heterozygous MYO1A may also be involved in this disorder due to the multigenic pattern of ARNSHL. Our data extend the mutation spectrum of PTPRQ and MYO1A, and have important implications for genetic counseling in unaffected sibs of this family. In addition, PTPRQ and MYO1A pathogenic variants have not to date been reported in the Iranian population.

PMID: 29308629 [PubMed]

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Neural representation of octave illusion in the human cortex revealed with functional magnetic resonance imaging

Publication date: Available online 8 January 2018
Source:Hearing Research
Author(s): Keita Tanaka, Hiroki Kurasaki, Shinya Kuriki
The auditory “octave illusion” arises when dichotic tones, presented one octave apart, alternate rapidly between the ears. This study aimed to explore the link between the perception of illusory pitches and brain activity during presentation of dichotic tones. We conducted a behavioral study of how participants perceived binaural dichotic tones of octave illusions and classified them, based on the reported percepts, in an illusion (ILL) group, without an illusion (non-ILL) group, and others. We recorded brain activity using functional magnetic resonance imaging and analyzed the activation due to dichotic illusion tones. The activation in the bilateral planum polare in the auditory cortex was significantly larger in the ILL group than in the non-ILL group. In the right premotor cortex, the non-ILL group showed a significantly larger activation than did the ILL group, suggesting that the sensation of the meter to the stimulus sound was significant in the non-ILL but not in the ILL group. The results indicated that the activity in these areas was related to the occurrence of octave illusions. The nonsignificant sensation of the meter to the stimulus sound in the ILL group may be consistent with the perception of octave illusion.



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Neural representation of octave illusion in the human cortex revealed with functional magnetic resonance imaging

Publication date: Available online 8 January 2018
Source:Hearing Research
Author(s): Keita Tanaka, Hiroki Kurasaki, Shinya Kuriki
The auditory “octave illusion” arises when dichotic tones, presented one octave apart, alternate rapidly between the ears. This study aimed to explore the link between the perception of illusory pitches and brain activity during presentation of dichotic tones. We conducted a behavioral study of how participants perceived binaural dichotic tones of octave illusions and classified them, based on the reported percepts, in an illusion (ILL) group, without an illusion (non-ILL) group, and others. We recorded brain activity using functional magnetic resonance imaging and analyzed the activation due to dichotic illusion tones. The activation in the bilateral planum polare in the auditory cortex was significantly larger in the ILL group than in the non-ILL group. In the right premotor cortex, the non-ILL group showed a significantly larger activation than did the ILL group, suggesting that the sensation of the meter to the stimulus sound was significant in the non-ILL but not in the ILL group. The results indicated that the activity in these areas was related to the occurrence of octave illusions. The nonsignificant sensation of the meter to the stimulus sound in the ILL group may be consistent with the perception of octave illusion.



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Neural representation of octave illusion in the human cortex revealed with functional magnetic resonance imaging

Publication date: Available online 8 January 2018
Source:Hearing Research
Author(s): Keita Tanaka, Hiroki Kurasaki, Shinya Kuriki
The auditory “octave illusion” arises when dichotic tones, presented one octave apart, alternate rapidly between the ears. This study aimed to explore the link between the perception of illusory pitches and brain activity during presentation of dichotic tones. We conducted a behavioral study of how participants perceived binaural dichotic tones of octave illusions and classified them, based on the reported percepts, in an illusion (ILL) group, without an illusion (non-ILL) group, and others. We recorded brain activity using functional magnetic resonance imaging and analyzed the activation due to dichotic illusion tones. The activation in the bilateral planum polare in the auditory cortex was significantly larger in the ILL group than in the non-ILL group. In the right premotor cortex, the non-ILL group showed a significantly larger activation than did the ILL group, suggesting that the sensation of the meter to the stimulus sound was significant in the non-ILL but not in the ILL group. The results indicated that the activity in these areas was related to the occurrence of octave illusions. The nonsignificant sensation of the meter to the stimulus sound in the ILL group may be consistent with the perception of octave illusion.



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Neural representation of octave illusion in the human cortex revealed with functional magnetic resonance imaging

Publication date: Available online 8 January 2018
Source:Hearing Research
Author(s): Keita Tanaka, Hiroki Kurasaki, Shinya Kuriki
The auditory “octave illusion” arises when dichotic tones, presented one octave apart, alternate rapidly between the ears. This study aimed to explore the link between the perception of illusory pitches and brain activity during presentation of dichotic tones. We conducted a behavioral study of how participants perceived binaural dichotic tones of octave illusions and classified them, based on the reported percepts, in an illusion (ILL) group, without an illusion (non-ILL) group, and others. We recorded brain activity using functional magnetic resonance imaging and analyzed the activation due to dichotic illusion tones. The activation in the bilateral planum polare in the auditory cortex was significantly larger in the ILL group than in the non-ILL group. In the right premotor cortex, the non-ILL group showed a significantly larger activation than did the ILL group, suggesting that the sensation of the meter to the stimulus sound was significant in the non-ILL but not in the ILL group. The results indicated that the activity in these areas was related to the occurrence of octave illusions. The nonsignificant sensation of the meter to the stimulus sound in the ILL group may be consistent with the perception of octave illusion.



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Neural representation of octave illusion in the human cortex revealed with functional magnetic resonance imaging

Publication date: Available online 8 January 2018
Source:Hearing Research
Author(s): Keita Tanaka, Hiroki Kurasaki, Shinya Kuriki
The auditory “octave illusion” arises when dichotic tones, presented one octave apart, alternate rapidly between the ears. This study aimed to explore the link between the perception of illusory pitches and brain activity during presentation of dichotic tones. We conducted a behavioral study of how participants perceived binaural dichotic tones of octave illusions and classified them, based on the reported percepts, in an illusion (ILL) group, without an illusion (non-ILL) group, and others. We recorded brain activity using functional magnetic resonance imaging and analyzed the activation due to dichotic illusion tones. The activation in the bilateral planum polare in the auditory cortex was significantly larger in the ILL group than in the non-ILL group. In the right premotor cortex, the non-ILL group showed a significantly larger activation than did the ILL group, suggesting that the sensation of the meter to the stimulus sound was significant in the non-ILL but not in the ILL group. The results indicated that the activity in these areas was related to the occurrence of octave illusions. The nonsignificant sensation of the meter to the stimulus sound in the ILL group may be consistent with the perception of octave illusion.



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