Pendred syndrome is an autosomal recessive disorder characterized by sensorineural hearing impairment, presence of goiter, and a partial defect in iodide organification, which may be associated with insufficient thyroid hormone synthesis. Goiter development (diffuse thyroid enlargement) and development of hypothyroidism are variable and depend on nutritional iodide intake. Pendred syndrome is caused by biallelic mutations in the SLC26A4 gene, which encodes pendrin, a transporter of chloride, bicarbonate and iodide. Mutations in this gene can also cause enlarged vestibular aqueduct (EVA).
The SLC26A4 gene (21 exons) spans ~57.2 kb of genomic DNA and is located on chromosome 7q22.3, ~108 Mb from the p-telomere. This P280-B3 SLC26A4 probemix contains one probe for each exon of the SLC26A4 gene. This probemix furthermore contains three mutation-specific probes for the L236P (707T>C; Exon 6; 382 nt) mutation, the IVS8+1G>A (Exon 8; 321 nt) donor splice mutation, and the T416P (1246A>C; Exon 10; 227 nt) amino acid substitution. These probes will only generate a signal when the mutation is present. These three mutations have been found in several cases of Pendred syndrome. In addition, 15 reference probes are included in this probemix, detecting several different autosomal chromosomal locations.
SD071 Sample DNA
Please note that the mutation-specific probes have only been tested on control plasmids and not on positive human DNA samples with the L236P mutation, IVS8+1G>A donor splice mutation, or the T416P amino acid substitution! This SD071 sample DNA is provided with each probemix vial and can be used in data binning in the fragment analysis and as a positive control for the mutation-specific probes (see page 2).
SALSA® MLPA® probemixes are designed to detect deletions/duplications of one or more sequences in the aforementioned gene in a DNA sample. Heterozygous deletions of recognition sequences should give a 35-50% reduced relative peak height of the amplification product of that probe. Note that a mutation or polymorphism (e.g. SNP) in the sequence detected by a probe can also cause a reduction in relative peak height, even when not located exactly on the ligation site! In addition, some probe signals are more sensitive to sample purity and small changes in experimental conditions. Therefore, deletions and duplications detected by MLPA should always be confirmed by other methods. Not all deletions and duplications detected by MLPA will be pathogenic; users should always verify the latest scientific literature when interpreting their findings. We have no information on what percentage of defects in these genes is caused by deletions/duplications of complete exons. Finally, note that most defects in this gene are expected to be small (point) mutations which will not be detected by this SALSA® MLPA® test.