@article {7748, title = {Usher syndrome: an effective sequencing approach to establish a genetic and clinical diagnosis.}, journal = {Hear Res}, volume = {320}, year = {2015}, month = {2015 Feb}, pages = {18-23}, abstract = {

Usher syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa, sensorineural hearing loss and, in some cases, vestibular dysfunction. The disorder is clinically and genetically heterogeneous and, to date, mutations in 11 genes have been described. This finding makes difficult to get a precise molecular diagnosis and offer patients accurate genetic counselling. To overcome this problem and to increase our knowledge of the molecular basis of Usher syndrome, we designed a targeted resequencing custom panel. In a first validation step a series of 16 Italian patients with known molecular diagnosis were analysed and 31 out of 32 alleles were detected (97\% of accuracy). After this step, 31 patients without a molecular diagnosis were enrolled in the study. Three out of them with an uncertain Usher diagnosis were excluded. One causative allele was detected in 24 out 28 patients (86\%) while the presence of both causative alleles characterized 19 patients out 28 (68\%). Sixteen novel and 27 known alleles were found in the following genes: USH2A (50\%), MYO7A (7\%), CDH23 (11\%), PCDH15 (7\%) and USH1G (2\%). Overall, on the 44 patients the protocol was able to characterize 74 alleles out of 88 (84\%). These results suggest that our panel is an effective approach for the genetic diagnosis of Usher syndrome leading to: 1) an accurate molecular diagnosis, 2) better genetic counselling, 3) more precise molecular epidemiology data fundamental for future interventional plans.

}, keywords = {Adult, Alleles, Cadherins, Extracellular Matrix Proteins, Female, Genetic Counseling, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Mutation, Myosins, Nerve Tissue Proteins, Usher Syndromes}, issn = {1878-5891}, doi = {10.1016/j.heares.2014.12.006}, author = {Lenarduzzi, S and Vozzi, D and Morgan, A and Rubinato, E and D{\textquoteright}Eustacchio, A and Osland, T M and Rossi, C and Graziano, C and Castorina, P and Ambrosetti, U and Morgutti, M and Girotto, G} } @article {3513, title = {Hereditary hearing loss: a 96 gene targeted sequencing protocol reveals novel alleles in a series of Italian and Qatari patients.}, journal = {Gene}, volume = {542}, year = {2014}, month = {2014 Jun 1}, pages = {209-16}, abstract = {

Deafness is a really common disorder in humans. It can begin at any age with any degree of severity. Hereditary hearing loss is characterized by a vast genetic heterogeneity with more than 140 loci described in humans but only 65 genes so far identified. Families affected by hearing impairment would have real advantages from an early molecular diagnosis that is of primary relevance in genetic counseling. In this perspective, here we report a family-based approach employing Ion Torrent DNA sequencing technology to analyze coding and UTR regions of 96 genes related to hearing function and loss in a first series of 12 families coming from Italy and Qatar. Using this approach we were able to find the causative gene in 4 out of these 12 families (33\%). In particular 5 novel alleles were identified in the following genes LOXHD1, TMPRSS3, TECTA and MYO15A already associated with hearing impairment. Our study confirms the usefulness of a targeted sequencing approach despite larger numbers are required for further validation and for defining a molecular epidemiology picture of hearing loss in these two countries.

}, keywords = {Alleles, Amino Acid Sequence, Carrier Proteins, Extracellular Matrix Proteins, Female, Genetic Testing, GPI-Linked Proteins, Hearing Loss, Humans, Italy, Male, Membrane Proteins, Molecular Sequence Data, Mutation, Myosins, Neoplasm Proteins, Pedigree, Qatar, Sequence Analysis, DNA, Serine Endopeptidases, Untranslated Regions}, issn = {1879-0038}, doi = {10.1016/j.gene.2014.03.033}, author = {Vozzi, D and Morgan, A and Vuckovic, D and D{\textquoteright}Eustacchio, A and Abdulhadi, K and Rubinato, E and Badii, R and Gasparini, P and Girotto, G} } @article {1953, title = {Two Novel COH1 Mutations in an Italian Patient with Cohen Syndrome.}, journal = {Mol Syndromol}, volume = {3}, year = {2012}, month = {2012 Jun}, pages = {30-33}, abstract = {

Cohen syndrome (CS) is an autosomal recessive disease caused by mutations in the COH1 gene. It is characterized by intellectual disability, hypotonia, joint hyperlaxity, severe myopia, characteristic facial dysmorphisms and, in some cases, intermittent isolated neutropenia. We investigated an Italian patient with CS together with his family. Genetic analysis disclosed 2 novel mutations: the first is an intronic mutation (c.8697-9A>G) creating a new splice site 8 nucleotides upstream, and the second is a duplication of 1 base (c.10156dupA) generating a premature stop codon. The compound heterozygous mutations explain the proband{\textquoteright}s phenotype and improved the knowledge of genotype-phenotype correlation.

}, issn = {1661-8769}, doi = {000338816}, author = {Athanasakis, E and Fabretto, A and Faletra, F and Mocenigo, M and Morgan, A and Gasparini, P} }