Splice-site mutation in thePDS gene may result in intrafamilial variability for deafness in Pendred syndrome

Solitary thyroid nodule as presenting symptom of Pendred syndrome caused by a novel splice-site mutation in intron 8 of the SLC26A4 gene

“…Pendrin defects result in neuroepithelial damage [5] and can cause inner ear malformations in which the upper coils of the cochlea form a common cavity (Mondini malformation) [9] and the vestibular aqueducts are dilated [14]. These anomalies result in a generally profound (>60 dB) sensorineural hearing loss usually of prelingual onset [7,10,12]. Our patient had a severe prelingual hearing loss with enlarged vestibular aqueducts and Mondini malformation on CT scanning of the temporal bones, a typical radiological marker of PDS.…”

“…PDS is caused by mutations in the SLC26A4 gene [4]. More than 50 different mutations have been described so far, accounting for part of the variability in clinical expression of the syndrome with a genotype-phenotype correlation observed for certain mutations [2,12,19]. Here, we report a 4-yearold boy with sensorineural hearing loss who presented with an isolated thyroid nodule in whom the clinical and molecular analysis resulted in the diagnosis of PDS caused by a mutation in intron 8 of the SLC26A4 gene.…”

Differential Diagnosis between Pendred and Pseudo-Pendred Syndromes: Clinical, Radiologic, and Molecular Studies

“…It is considered the most common cause of congenital deafness, but the actual incidence of the syndrome is difficult to establish because of the variable phenotype of affected subjects, even within the same family (2)(3)(4). In the last 3 y PS has been associated, with a homozygous or compound heterozygous pattern, to mutations in the PDS gene (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). PDS maps on chromosome band 7q22-31.1 and codes for pendrin (7), a transmembrane protein, which was first found to be expressed in the thyroid and in particular at the apical surface of the thyroid cell, where it likely functions as an iodide-chloride transporter (15)(16)(17).…”

Genetics of Nonsyndromic Recessively Inherited Moderate to Severe and Progressive Deafness in Humans

“…In other instances, presence of missense or nonsense mutations in the same gene have been associated with variability in degree of hearing loss (Pennings et al, 2004). Additionally, some mutations creating new cryptic splice sites within genes have also been associated with intra-familial variability of hearing loss (Lopez-Bigas et al, 1999). However, in some instances there are no genotype-phenotype correlations.…”

“…Considerable residual hearing is present in some affected individuals who are homozygous for mutations creating new splice sites in SLC26A4 (Lopez-Bigas et al, 1999;Naz, 2001). These two described mutations create splice sites a few nucleotides away from the canonical donor sites, and support the hypothesis that variable degree of hearing loss in SLC26A4 linked families may indicate splice site mutations.…”