Pendred syndrome ... (Pendred syndrome) - Gen SLC26A4
The Pendred syndrome is a disease characterized by the association of hearing loss and impaired thyroid, goiter-hearing. When thyroid goiter develops in a person with Pendred syndrome usually it appears in late childhood and adult initial stage. In most cases, thyroid enlargement causes the thyroid gland to malfunction. In most people with Pendred syndrome, sensorineural deafness is evident at birth. In other cases, hearing loss does not develop until later in infancy or early childhood. There are also frequent other abnormalities of the inner ear. Some affected individuals have balance problems due to vestibular system dysfunction. In addition, in people affected the vestibular aqueduct is unusually large. A characteristic feature of the syndrome is an enlarged vestibular aqueduct (EVA), but not the cause of hearing loss in people with this syndrome. Some affected individuals also have an abnormal cochlea. The combination of an enlarged vestibular aqueduct and cochlea abnormally known as Mondini malformation.
Pendred syndrome the shares features with other processes in the thyroid and hearing loss. It is unclear whether these processes are considered different entities or are part of a spectrum of signs and symptoms related. These processes include a non - syndromic hearing loss (hearing loss does not affect other parts of the body) called DFNB4 and in a small number of people, a form of congenital hypothyroidism due to thyroid hypoplasia. All of these entities are due to mutations in the same gene.
The Pendred syndrome is due to mutations in the SLC26A4 gene (solute carrier family 26 member 4), located on the long arm of chromosome 7 (7q31). This gene encodes the protein pendrin. This protein carries ions, including chloride, iodide, and bicarbonate, inside and outside the cells. Although pendrin function is not fully understood, this protein is important for normal thyroid function and inner ear. In the thyroid, probably it carries pendrin iodide ions out of cells. The binding of iodide ions at one thyroglobulin protein is an important step production of thyroid hormones. In the inner ear, the pendrin probably helps control proper balance of particles as chloride and bicarbonate ions. Maintaining the correct concentrations of these ions is essential for the hearing process and to determine the amount of fluid that bathes the inner ear. The liquid level seems particularly important during development of the inner ear, and may influence the shape of the bony structures such as the cochlea and vestibular aqueduct.
They have identified more than 150 mutations in the SLC26A4 gene in individuals with Pendred syndrome. Some of these mutations change the amino acids used for synthesizing the pendrin protein. Mutations in the gene, alter the structure or function of the pendrin, which interrupts the transport of ions, causing the thyroid tissue may increase in size to compensate for the apparent lack of iodine. In the inner ear, impaired activity pendrin probably alters the balance of ions and fluid levels. These changes are likely to disrupt the development of structures in the inner ear and lead to hearing loss.
In particular populations, certain mutations occur more frequently. For example, a common gene mutation in the Japanese population replaces the amino acid histidine by the amino acid arginine at position 723 in the pendrin. Among Northern Europeans, frequent mutations in the amino acid threonine replaced by the amino acid proline at position 416 of the protein or replace the amino acid leucine by proline at position 236. Other mutations alter the gene by deleting or adding a small amount of DNA. These deletions and additions likely create a premature stop signal in coding pendrin, causing an abnormally small protein.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Pendred syndrome, by complete PCR amplification of exons SLC26A4 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).