Abstract
Hereditary Hearing Loss (HHL) is an extremely heterogeneous disorder. Approximately 30 out of 80 known HHL genes are associated with autosomal dominant forms. Here, we identified PSIP1/LEDGF (isoform p75) as a novel strong candidate gene involved in dominant HHL. Using exome sequencing we found a frameshift deletion (c.1554-1555del leading to p.E518Dfs∗2) in an Italian pedigree affected by sensorineural mild-to-moderate HHL but also showing a variable eye phenotype (i.e. uveitis, optic neuropathy). This deletion led to a premature stop codon (p.T519X) with truncation of the last 12 amino acids. PSIP1 was recently described as a transcriptional co-activator regulated by miR-135b in vestibular hair cells of the mouse inner ear as well as a possible protector against photoreceptor degeneration. Here, we demonstrate that it is ubiquitously expressed in the mouse inner ear. The PSIP1 mutation is associated with a peculiar audiometric slope toward the high frequencies. These findings indicate that PSIP1 likely plays an important role in HHL.
| Original language | English |
|---|---|
| Article number | 18568 |
| Journal | Scientific Reports |
| Volume | 5 |
| DOIs | |
| Publication status | Published - Dec 22 2015 |
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ASJC Scopus subject areas
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Cite this
PSIP1/LEDGF : A new gene likely involved in sensorineural progressive hearing loss. / Girotto, Giorgia; Scheffer, Déborah I.; Morgan, Anna; Vozzi, Diego; Rubinato, Elisa; Di Stazio, Mariateresa; Muzzi, Enrico; Pensiero, Stefano; Giersch, Anne B.; Corey, David P.; Gasparini, Paolo.
In: Scientific Reports, Vol. 5, 18568, 22.12.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PSIP1/LEDGF
T2 - A new gene likely involved in sensorineural progressive hearing loss
AU - Girotto, Giorgia
AU - Scheffer, Déborah I.
AU - Morgan, Anna
AU - Vozzi, Diego
AU - Rubinato, Elisa
AU - Di Stazio, Mariateresa
AU - Muzzi, Enrico
AU - Pensiero, Stefano
AU - Giersch, Anne B.
AU - Corey, David P.
AU - Gasparini, Paolo
PY - 2015/12/22
Y1 - 2015/12/22
N2 - Hereditary Hearing Loss (HHL) is an extremely heterogeneous disorder. Approximately 30 out of 80 known HHL genes are associated with autosomal dominant forms. Here, we identified PSIP1/LEDGF (isoform p75) as a novel strong candidate gene involved in dominant HHL. Using exome sequencing we found a frameshift deletion (c.1554-1555del leading to p.E518Dfs∗2) in an Italian pedigree affected by sensorineural mild-to-moderate HHL but also showing a variable eye phenotype (i.e. uveitis, optic neuropathy). This deletion led to a premature stop codon (p.T519X) with truncation of the last 12 amino acids. PSIP1 was recently described as a transcriptional co-activator regulated by miR-135b in vestibular hair cells of the mouse inner ear as well as a possible protector against photoreceptor degeneration. Here, we demonstrate that it is ubiquitously expressed in the mouse inner ear. The PSIP1 mutation is associated with a peculiar audiometric slope toward the high frequencies. These findings indicate that PSIP1 likely plays an important role in HHL.
AB - Hereditary Hearing Loss (HHL) is an extremely heterogeneous disorder. Approximately 30 out of 80 known HHL genes are associated with autosomal dominant forms. Here, we identified PSIP1/LEDGF (isoform p75) as a novel strong candidate gene involved in dominant HHL. Using exome sequencing we found a frameshift deletion (c.1554-1555del leading to p.E518Dfs∗2) in an Italian pedigree affected by sensorineural mild-to-moderate HHL but also showing a variable eye phenotype (i.e. uveitis, optic neuropathy). This deletion led to a premature stop codon (p.T519X) with truncation of the last 12 amino acids. PSIP1 was recently described as a transcriptional co-activator regulated by miR-135b in vestibular hair cells of the mouse inner ear as well as a possible protector against photoreceptor degeneration. Here, we demonstrate that it is ubiquitously expressed in the mouse inner ear. The PSIP1 mutation is associated with a peculiar audiometric slope toward the high frequencies. These findings indicate that PSIP1 likely plays an important role in HHL.
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UR - http://www.scopus.com/inward/citedby.url?scp=84951756451&partnerID=8YFLogxK
U2 - 10.1038/srep18568
DO - 10.1038/srep18568
M3 - Article
AN - SCOPUS:84951756451
VL - 5
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 18568
ER -