Pendred Syndrome, or Not Pendred Syndrome? That Is the Question

Genes

Sofia Fiorino¹  Paola Tesolin²  Giorgia Girotto²  Daniele Dell’Orco³  Stefania Lenarduzzi⁴  Eva Orzan⁴  Anna Morgan⁴  Veronica Castro⁴  Claudio Granata⁴  Elisabetta Cattaruzzi⁴  Lydie Ammar⁴  Elisa Rubinato⁴ 

[1] Department of Life Sciences, University of Trieste, 34127 Trieste, Italy;Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy;Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biological Chemistry, University of Verona, 37129 Verona, Italy;Institute for Maternal and Child Health—IRCCS, Burlo Garofolo, 34127 Trieste, Italy;

关键词: Pendred syndrome;    Whole-Exome Sequencing;    genotype-phenotype correlation;   

DOI  :  10.3390/genes12101569

来源: DOAJ

【 摘 要 】

Pendred syndrome (PDS) is the most common form of syndromic Hearing Loss (HL), characterized by sensorineural HL, inner ear malformations, and goiter, with or without hypothyroidism. SLC26A4 is the major gene involved, even though ~50% of the patients carry only one pathogenic mutation. This study aims to define the molecular diagnosis for a cohort of 24 suspected-PDS patients characterized by a deep radiological and audiological evaluation. Whole-Exome Sequencing (WES), the analysis of twelve variants upstream of SLC26A4, constituting the “CEVA haplotype” and Multiplex Ligation Probe Amplification (MLPA) searching for deletions/duplications in SLC26A4 gene have been carried out. In five patients (20.8%) homozygous/compound heterozygous SLC26A4 mutations, or pathogenic mutation in trans with the CEVA haplotype have been identified, while five subjects (20.8%) resulted heterozygous for a single variant. In silico protein modeling supported the pathogenicity of the detected variants, suggesting an effect on the protein stabilization/function. Interestingly, we identified a genotype-phenotype correlation among those patients carrying SLC26A4 mutations, whose audiograms presented a characteristic slope at the medium and high frequencies, providing new insights into PDS. Finally, an interesting homozygous variant in MYO5C has been identified in one patient negative to SLC26A4 gene, suggesting the identification of a new HL candidate gene.

【 授权许可】

Unknown