Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.7.48 (
transcriptase
)
9,479
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
PTPRQ
Trp2294*
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.
...
PMID:A C-terminal nonsense mutation links PTPRQ with autosomal-dominant hearing loss, DFNA73. 2930 2
