title: Further characterisation of the recently described SLC26A4 c.918+2T>C mutation and reporting of a novel variant predicted to be damaging.
abstract: Pendred syndrome (PS) is the second most common type of autosomal recessive syndromic hearing loss (HL). It is characterised by sensorineural HL and goiter with occasional hypothyroidism. These features are generally accompanied by malformations of the inner ear, as enlarged vestibular aqueduct (EVA). In about 50% of probands, mutations in the SLC26A4 gene are the cause of the disease. Here we report the case of a Portuguese female, aged 47, presenting with severe to profound HL and hypothyroidism. Her mother and sister, both deceased, had suffered from HL and goiter. By MRI and CT, an enlarged vestibular aqueduct and endolymphatic sac were observed. Molecular study of the patient included screening for GJB2 coding mutations and GJB6 common deletions followed by screening of all SLC26A4 exons, as well as intronic regions 8 and 14. Mutation c.918+2T>C was found for the first time in homozygosity in the intronic region 7 of the SLC26A4 gene. Whilst sequencing the control samples, a novel mutation c.821C>G was found in heterozygosity in the exon 7 of SLC26A4 gene and was predicted to be damaging. This study thus led to the finding of two novel SLC26A4 genotypes and provides new insight on the phenotypic features associated with PS.
authors.affiliation: BioISI - Biosystems & Integrative Sciences Institute, Faculty of Science of the University of Lisbon, Portugal, * Present address: UCL Ear Institute, London, United Kingdom;
authors.forename: A C
authors.initials: AC
authors.lastname: Gonçalves
authors.affiliation: ENT-CHLO, HEM, ENT Service, Centro Hospitalar de Lisboa Ocidental EPE, Egas Moniz Hospital, Portugal;
authors.forename: R
authors.initials: R
authors.lastname: Santos
authors.affiliation: ENT-CHLO, HEM, ENT Service, Centro Hospitalar de Lisboa Ocidental EPE, Egas Moniz Hospital, Portugal;|FCM/UNL, Department of Anatomy, Nova Medical School, New University of Lisbon, Portugal;
authors.forename: A
authors.initials: A
authors.lastname: O'Neill
authors.affiliation: ENT-CHLO, HEM, ENT Service, Centro Hospitalar de Lisboa Ocidental EPE, Egas Moniz Hospital, Portugal;
authors.forename: P
authors.initials: P
authors.lastname: Escada
authors.affiliation: BioISI - Biosystems & Integrative Sciences Institute, Faculty of Science of the University of Lisbon, Portugal, * Present address: UCL Ear Institute, London, United Kingdom;
authors.forename: G
authors.initials: G
authors.lastname: Fialho
authors.affiliation: BioISI - Biosystems & Integrative Sciences Institute, Faculty of Science of the University of Lisbon, Portugal, * Present address: UCL Ear Institute, London, United Kingdom;|ESS/IPS, School of Health, Polytechnic Institute of Setúbal, Portugal.
authors.forename: H
authors.initials: H
authors.lastname: Caria
mesh_terms: D005260:Female; D014644:Genetic Variation; D006044:Goiter, Nodular / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D000076988:Sulfate Transporters
chemical_list: D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters
keywords: Berkeley Drosophila Genome Project (BDGP); Computerised tomography (CT); Enlarged vestibular aqueduct (EVA); Hearing loss (HL); Magnetic resonance imaging (MRI); Pendred syndrome (PS); Videonystagmography (VNG)