TY - JOUR T1 - Targeted sequencing identifies novel variants involved in autosomal recessive hereditary hearing loss in Qatari families. JF - Mutat Res Y1 - 2017 A1 - Alkowari, Moza K A1 - Vozzi, Diego A1 - Bhagat, Shruti A1 - Krishnamoorthy, Navaneethakrishnan A1 - Morgan, Anna A1 - Hayder, Yousra A1 - Logendra, Barathy A1 - Najjar, Nehal A1 - Gandin, Ilaria A1 - Gasparini, Paolo A1 - Badii, Ramin A1 - Girotto, Giorgia A1 - Abdulhadi, Khalid KW - Adolescent KW - Alleles KW - Cadherins KW - Child KW - Child, Preschool KW - Connexins KW - Female KW - GPI-Linked Proteins KW - Hearing Loss, Sensorineural KW - Humans KW - Infant KW - Male KW - Membrane Proteins KW - Models, Molecular KW - Mutation KW - Myosin Heavy Chains KW - Pedigree KW - Protein Conformation KW - Qatar KW - Sequence Analysis, DNA AB -

Hereditary hearing loss is characterized by a very high genetic heterogeneity. In the Qatari population the role of GJB2, the worldwide HHL major player, seems to be quite limited compared to Caucasian populations. In this study we analysed 18 Qatari families affected by non-syndromic hearing loss using a targeted sequencing approach that allowed us to analyse 81 genes simultaneously. Thanks to this approach, 50% of these families (9 out of 18) resulted positive for the presence of likely causative alleles in 6 different genes: CDH23, MYO6, GJB6, OTOF, TMC1 and OTOA. In particular, 4 novel alleles were detected while the remaining ones were already described to be associated to HHL in other ethnic groups. Molecular modelling has been used to further investigate the role of novel alleles identified in CDH23 and TMC1 genes demonstrating their crucial role in Ca2+ binding and therefore possible functional role in proteins. Present study showed that an accurate molecular diagnosis based on next generation sequencing technologies might largely improve molecular diagnostics outcome leading to benefits for both genetic counseling and definition of recurrence risk.

VL - 800-802 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28501645?dopt=Abstract ER -