Lights and Shadows in the Genetics of Syndromic and Non-Syndromic Hearing Loss in the Italian Population

• Main Authors: Anna Morgan, Stefania Lenarduzzi, Beatrice Spedicati, Elisabetta Cattaruzzi, Flora Maria Murru, Giulia Pelliccione, Daniela Mazzà, Marcella Zollino, Claudio Graziano, Umberto Ambrosetti, Marco Seri, Flavio Faletra, Giorgia Girotto
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Genes
• Subjects: hereditary hearing loss; MLPA; whole exome sequencing; molecular diagnosis
• Online Access: https://www.mdpi.com/2073-4425/11/11/1237

Hearing loss (HL), both syndromic (SHL) and non-syndromic (NSHL), is the most common sensory disorder, affecting ~460 million people worldwide. More than 50% of the congenital/childhood cases are attributable to genetic causes, highlighting the importance of genetic testing in this class of disorders. Here we applied a multi-step strategy for the molecular diagnosis of HL in 125 patients, which included: (1) an accurate clinical evaluation, (2) the analysis of <i>GJB2, GJB6,</i> and <i>MT-RNR1</i> genes, (3) the evaluation <i>STRC-CATSPER2</i> and <i>OTOA</i> deletions via Multiplex Ligation Probe Amplification (MLPA), (4) Whole Exome Sequencing (WES) in patients negative to steps 2 and 3. Our approach led to the characterization of 50% of the NSHL cases, confirming both the relevant role of the <i>GJB2</i> (20% of cases) and <i>STRC</i> deletions (6% of cases), and the high genetic heterogeneity of NSHL. Moreover, due to the genetic findings, 4% of apparent NSHL patients have been re-diagnosed as SHL. Finally, WES characterized 86% of SHL patients, supporting the role of already know disease-genes. Overall, our approach proved to be efficient in identifying the molecular cause of HL, providing essential information for the patients’ future management.