Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss

Giorgia Girotto, Khalid Abdulhadi, Annalisa Buniello, Diego Vozzi, Danilo Licastro, Angela D'Eustacchio, Dragana Vuckovic, Moza K. Al-Kowari, Karen P. Steel, Ramin Badii, Paolo Gasparini

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article numbere80323
JournalPLoS One
Volume8
Issue number12
DOIs
Publication statusPublished - 2 Dec 2013

Fingerprint

Exome
Audition
hearing
Hearing Loss
linkage (genetics)
deafness
mutation
Mutation
Genes
Deafness
Elongation
RNA Polymerase III
Peptide Initiation Factors
Endothelial cells
Transcription Factor TFIIIB
Transcription
Chromosomes
Cochlear Duct
Ducts
Stria Vascularis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Girotto, G., Abdulhadi, K., Buniello, A., Vozzi, D., Licastro, D., D'Eustacchio, A., ... Gasparini, P. (2013). Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. PLoS One, 8(12), [e80323]. https://doi.org/10.1371/journal.pone.0080323

Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. / Girotto, Giorgia; Abdulhadi, Khalid; Buniello, Annalisa; Vozzi, Diego; Licastro, Danilo; D'Eustacchio, Angela; Vuckovic, Dragana; Al-Kowari, Moza K.; Steel, Karen P.; Badii, Ramin; Gasparini, Paolo.

In: PLoS One, Vol. 8, No. 12, e80323, 02.12.2013.

Research output: Contribution to journalArticle

Girotto, G, Abdulhadi, K, Buniello, A, Vozzi, D, Licastro, D, D'Eustacchio, A, Vuckovic, D, Al-Kowari, MK, Steel, KP, Badii, R & Gasparini, P 2013, 'Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss', PLoS One, vol. 8, no. 12, e80323. https://doi.org/10.1371/journal.pone.0080323
Girotto, Giorgia ; Abdulhadi, Khalid ; Buniello, Annalisa ; Vozzi, Diego ; Licastro, Danilo ; D'Eustacchio, Angela ; Vuckovic, Dragana ; Al-Kowari, Moza K. ; Steel, Karen P. ; Badii, Ramin ; Gasparini, Paolo. / Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss. In: PLoS One. 2013 ; Vol. 8, No. 12.
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