Hereditary hearing loss in Italian and Qatari population: identification of new deafness genes using high throughput technologies
Giorgia Girotto1, Moza Alkowari2, Khalid Abdulhadi3, Savina Dipresa1, Diego Vozzi4, Danilo Licastro4, Emmanouil Athanasakis1, Rowa Siam2, Nihal Najjar2, Ramin Badii2 and Paolo Gasparini1
1Med Genet, IRCCS-Burlo Garofolo Children Hospital, Trieste Univ, Trieste, Italy
2 Molecular Genetics Laboratory, Hamad Medical Corporation, Doha, Qatar
3ENT Division, Hamad Medical Corporation, Doha, Qatar
4CBM scrl., Basovizza, Trieste, Italy
Hereditary Hearing loss (HLL) is a common disorder accounting for at least 60% of prelingual deafness. Most cases (70%) are non-syndromic (NSHHL) while the others (15-30%) are syndromic in which there are other clinical features in addition to the hearing impairment. GJB2 gene mutations, GJB6 deletion, and A1555G mitochondrial mutation play a major role worldwide and account for approximately 35% of Italian pathogenic alleles and almost no other common genes have been identified. Regarding the Qatari population, a molecular screening for these common genes/mutations on 126 Qatari patients clearly demonstrates that GJB2, GJB6 deletion and A1555G accounts for a minor proportion of NSHHL cases in this population.
Thus, these findings strongly suggest that many genes for NSHHL await identification and, until recently, linkage analysis was the first step in positional cloning approaches. Now, the availability of Next Generation Sequencing (NGS) technologies opens new perspectives in the search for causative genes. In this light, to increase our knowledge on the molecular bases of HHL in the Italian and Qatari populations, an extensive use of high throughput technologies such as High Density arrays (i.e for linkage data) and Next Generation Sequencing has been planned.
Six Italian families (dominant inheritance) and five Qatari families (recessive inheritance), all negative for the presence of mutations in the most common hearing genes, have been selected. High density SNPs arrays have been utilized to define a minimum number of candidate loci, to be applied in the filtering phase of NGS data. NGS protocols have been used to obtain whole exome data. After filtering (dbSNP and in-house database), some candidate genes have been identified in both populations. Results have been validated by Sanger sequencing and should be further investigated at the functional level. These results will definitely increase our knowledge of new deafness genes, and further confirm the importance of such new technologies for disease gene identification.
