Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss.
Nonsyndromic Hereditary Hearing Loss is a common disorder accounting for at least 60% of prelingual deafness. GJB2 gene mutations, GJB6 deletion, and the A1555G mitochondrial mutation play a major role worldwide in causing deafness, but there is a high degree of genetic heterogeneity and many genes...
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doaj-6f98223b1aec499baed0ab3f0863ba012020-11-24T22:08:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8032310.1371/journal.pone.0080323Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss.Giorgia GirottoKhalid AbdulhadiAnnalisa BunielloDiego VozziDanilo LicastroAngela d'EustacchioDragana VuckovicMoza Khalifa AlkowariKaren P SteelRamin BadiiPaolo GaspariniNonsyndromic Hereditary Hearing Loss is a common disorder accounting for at least 60% of prelingual deafness. GJB2 gene mutations, GJB6 deletion, and the A1555G mitochondrial mutation play a major role worldwide in causing deafness, but there is a high degree of genetic heterogeneity and many genes involved in deafness have not yet been identified. Therefore, there remains a need to search for new causative mutations. In this study, a combined strategy using both linkage analysis and sequencing identified a new mutation causing hearing loss. Linkage analysis identified a region of 40 Mb on chromosome 5q13 (LOD score 3.8) for which exome sequencing data revealed a mutation (c.7873 T>G leading to p.*2625Gluext*11) in the BDP1 gene (B double prime 1, subunit of RNA polymerase III transcription initiation factor IIIB) in patients from a consanguineous Qatari family of second degree, showing bilateral, post-lingual, sensorineural moderate to severe hearing impairment. The mutation disrupts the termination codon of the transcript resulting in an elongation of 11 residues of the BDP1 protein. This elongation does not contain any known motif and is not conserved across species. Immunohistochemistry studies carried out in the mouse inner ear showed Bdp1 expression within the endothelial cells in the stria vascularis, as well as in mesenchyme-derived cells surrounding the cochlear duct. The identification of the BDP1 mutation increases our knowledge of the molecular bases of Nonsyndromic Hereditary Hearing Loss and provides new opportunities for the diagnosis and treatment of this disease in the Qatari population.http://europepmc.org/articles/PMC3846559?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Giorgia Girotto Khalid Abdulhadi Annalisa Buniello Diego Vozzi Danilo Licastro Angela d'Eustacchio Dragana Vuckovic Moza Khalifa Alkowari Karen P Steel Ramin Badii Paolo Gasparini |
spellingShingle |
Giorgia Girotto Khalid Abdulhadi Annalisa Buniello Diego Vozzi Danilo Licastro Angela d'Eustacchio Dragana Vuckovic Moza Khalifa Alkowari Karen P Steel Ramin Badii Paolo Gasparini Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. PLoS ONE |
author_facet |
Giorgia Girotto Khalid Abdulhadi Annalisa Buniello Diego Vozzi Danilo Licastro Angela d'Eustacchio Dragana Vuckovic Moza Khalifa Alkowari Karen P Steel Ramin Badii Paolo Gasparini |
author_sort |
Giorgia Girotto |
title |
Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. |
title_short |
Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. |
title_full |
Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. |
title_fullStr |
Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. |
title_full_unstemmed |
Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. |
title_sort |
linkage study and exome sequencing identify a bdp1 mutation associated with hereditary hearing loss. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Nonsyndromic Hereditary Hearing Loss is a common disorder accounting for at least 60% of prelingual deafness. GJB2 gene mutations, GJB6 deletion, and the A1555G mitochondrial mutation play a major role worldwide in causing deafness, but there is a high degree of genetic heterogeneity and many genes involved in deafness have not yet been identified. Therefore, there remains a need to search for new causative mutations. In this study, a combined strategy using both linkage analysis and sequencing identified a new mutation causing hearing loss. Linkage analysis identified a region of 40 Mb on chromosome 5q13 (LOD score 3.8) for which exome sequencing data revealed a mutation (c.7873 T>G leading to p.*2625Gluext*11) in the BDP1 gene (B double prime 1, subunit of RNA polymerase III transcription initiation factor IIIB) in patients from a consanguineous Qatari family of second degree, showing bilateral, post-lingual, sensorineural moderate to severe hearing impairment. The mutation disrupts the termination codon of the transcript resulting in an elongation of 11 residues of the BDP1 protein. This elongation does not contain any known motif and is not conserved across species. Immunohistochemistry studies carried out in the mouse inner ear showed Bdp1 expression within the endothelial cells in the stria vascularis, as well as in mesenchyme-derived cells surrounding the cochlear duct. The identification of the BDP1 mutation increases our knowledge of the molecular bases of Nonsyndromic Hereditary Hearing Loss and provides new opportunities for the diagnosis and treatment of this disease in the Qatari population. |
url |
http://europepmc.org/articles/PMC3846559?pdf=render |
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