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Hearing Disorders: HELP
Articles by Stefano Duga
Based on 3 articles published since 2010
(Why 3 articles?)
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Between 2010 and 2020, Stefano Duga wrote the following 3 articles about Hearing Disorders.
 
+ Citations + Abstracts
1 Article First independent replication of the involvement of LARS2 in Perrault syndrome by whole-exome sequencing of an Italian family. 2016

Soldà, Giulia / Caccia, Sonia / Robusto, Michela / Chiereghin, Chiara / Castorina, Pierangela / Ambrosetti, Umberto / Duga, Stefano / Asselta, Rosanna. ·Department of Biomedical Sciences, Humanitas University, Milan, Italy. · Humanitas Clinical and Research Center, Milan, Italy. · Department of Biomedical and Clinical Sciences "Luigi Sacco", Università degli Studi di Milano - LITA Vialba, Milan, Italy. · UO Audiologia, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. · Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milan, Italy. ·J Hum Genet · Pubmed #26657938.

ABSTRACT: Perrault syndrome (MIM #233400) is a rare autosomal recessive disorder characterized by ovarian dysgenesis and primary ovarian insufficiency in females, and progressive hearing loss in both genders. Recently, mutations in five genes (HSD17B4, HARS2, CLPP, LARS2 and C10ORF2) were found to be responsible for Perrault syndrome, although they do not account for all cases of this genetically heterogeneous condition. We used whole-exome sequencing to identify pathogenic variants responsible for Perrault syndrome in an Italian pedigree with two affected siblings. Both patients were compound heterozygous for two novel missense variants within the mitochondrial leucyl-tRNA synthetase (LARS2): NM_015340.3:c.899C>T(p.Thr300Met) and c.1912G>A(p.Glu638Lys). Both variants cosegregated with the phenotype in the family. p.Thr300 and p.Glu638 are evolutionarily conserved residues, and are located, respectively, within the editing domain and immediately before the catalytically important KMSKS motif. Homology modeling using as template the E. coli leucyl-tRNA synthetase provided further insights on the possible pathogenic effects of the identified variants. This represents the first independent replication of the involvement of LARS2 mutations in Perrault syndrome, contributing valuable information for the further understanding of this disease.

2 Article The expanding spectrum of PRPS1-associated phenotypes: three novel mutations segregating with X-linked hearing loss and mild peripheral neuropathy. 2015

Robusto, Michela / Fang, Mingyan / Asselta, Rosanna / Castorina, Pierangela / Previtali, Stefano C / Caccia, Sonia / Benzoni, Elena / De Cristofaro, Raimondo / Yu, Cong / Cesarani, Antonio / Liu, Xuanzhu / Li, Wangsheng / Primignani, Paola / Ambrosetti, Umberto / Xu, Xun / Duga, Stefano / Soldà, Giulia. ·Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milan, Italy. · BGI-Shenzhen, Shenzhen, China. · Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UO Audiologia, Milan, Italy. · Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy. · Laboratory of Medical Genetics, Molecular Genetic Sector, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. · Haemostasis Research Center, Institute of Internal Medicine and Geriatrics, Catholic University School of Medicine, Rome, Italy. ·Eur J Hum Genet · Pubmed #25182139.

ABSTRACT: Next-generation sequencing is currently the technology of choice for gene/mutation discovery in genetically-heterogeneous disorders, such as inherited sensorineural hearing loss (HL). Whole-exome sequencing of a single Italian proband affected by non-syndromic HL identified a novel missense variant within the PRPS1 gene (NM_002764.3:c.337G>T (p.A113S)) segregating with post-lingual, bilateral, progressive deafness in the proband's family. Defects in this gene, encoding the phosphoribosyl pyrophosphate synthetase 1 (PRS-I) enzyme, determine either X-linked syndromic conditions associated with hearing impairment (eg, Arts syndrome and Charcot-Marie-Tooth neuropathy type X-5) or non-syndromic HL (DFNX1). A subsequent screening of the entire PRPS1 gene in 16 unrelated probands from X-linked deaf families led to the discovery of two additional missense variants (c.343A>G (p.M115V) and c.925G>T (p.V309F)) segregating with hearing impairment, and associated with mildly-symptomatic peripheral neuropathy. All three variants result in a marked reduction (>60%) of the PRS-I activity in the patients' erythrocytes, with c.343A>G (p.M115V) and c.925G>T (p.V309F) affecting more severely the enzyme function. Our data significantly expand the current spectrum of pathogenic variants in PRPS1, confirming that they are associated with a continuum disease spectrum, thus stressing the importance of functional studies and detailed clinical investigations for genotype-phenotype correlation.

3 Article A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing. 2012

Soldà, Giulia / Robusto, Michela / Primignani, Paola / Castorina, Pierangela / Benzoni, Elena / Cesarani, Antonio / Ambrosetti, Umberto / Asselta, Rosanna / Duga, Stefano. ·Dipartimento di Biologia e Genetica per Scienze Mediche, Università degli Studi di Milano, Milan, Italy. giulia.solda@unimi.it ·Hum Mol Genet · Pubmed #22038834.

ABSTRACT: The miR-96, miR-182 and miR-183 microRNA (miRNA) family is essential for differentiation and function of the vertebrate inner ear. Recently, point mutations within the seed region of miR-96 were reported in two Spanish families with autosomal dominant non-syndromic sensorineural hearing loss (NSHL) and in a mouse model of NSHL. We screened 882 NSHL patients and 836 normal-hearing Italian controls and identified one putative novel mutation within the miR-96 gene in a family with autosomal dominant NSHL. Although located outside the mature miR-96 sequence, the detected variant replaces a highly conserved nucleotide within the companion miR-96*, and is predicted to reduce the stability of the pre-miRNA hairpin. To evaluate the effect of the detected mutation on miR-96/mir-96* biogenesis, we investigated the maturation of miR-96 by transient expression in mammalian cells, followed by real-time reverse-transcription polymerase chain reaction (PCR). We found that both miR-96 and miR-96* levels were significantly reduced in the mutant, whereas the precursor levels were unaffected. Moreover, miR-96 and miR-96* expression levels could be restored by a compensatory mutation that reconstitutes the secondary structure of the pre-miR-96 hairpin, demonstrating that the mutation hinders precursor processing, probably interfering with Dicer cleavage. Finally, even though the mature miR-96 sequence is not altered, we demonstrated that the identified mutation significantly impacts on miR-96 regulation of selected targets. In conclusion, we provide further evidence of the involvement of miR-96 mutations in human deafness and demonstrate that a quantitative defect of this miRNA may contribute to NSHL.