nPendred syndrome （PS） is characterized by autosomal recessive inheritance of goiter associated with a defect of iodide organification, hearing loss, enlargement of the vestibular aqueduct （EVA）, and mutations of ...nPendred syndrome （PS） is characterized by autosomal recessive inheritance of goiter associated with a defect of iodide organification, hearing loss, enlargement of the vestibular aqueduct （EVA）, and mutations of the SLC26A4 gene. However, not all EVA patients have PS or SLC26A4 mutations. Two mutant alleles of SLC26A4 are detected in 1/4 of North American or European EVA populations, one mutant allele is detected in another 1/4 of patient populations, and no mutations are de-tected in the other 1/2. The presence of two mutant al-leles of SLC26A4 is associated with abnormal iodide or-ganification, increased thyroid gland volume, increased severity of hearing loss, and bilateral EVA. The pres-ence of a single mutant allele of SLC26A4 is associated with normal iodide organification, normal thyroid gland volume, less severe hearing loss and either bilateral or unilateral EVA. When other underlying correlations are accounted for, the presence of a cochlear malformation or the size of EVA does not have an effect on hearing thresholds. This is consistent with observations of an Slc26a4 mutant mouse model of EVA in which hearing loss is independent of endolymphatic hydrops or in-ner ear malformations. Segregation analyses of EVA in families suggest that the patients carrying one mutant allele of SLC26A4 have a second, undetected mutant allele of SLC26A4, and the probability of a sibling hav-ing EVA is consistent with its segregation as an autoso-mal recessive trait. Patients without any mutations are an etiologically heterogeneous group in which siblings have a lower probability of having EVA. SLC26A4 muta-tion testing can provide prognostic information to guide clinical surveillance and management, as well as the probability of EVA affecting a sibling.展开更多
基金Supported by NIH intramural research funds Z01-DC-000039,Z01-DC-000060 and Z01-DC-000064,NIH grants R01-DK43495 and P30-DK34854Kansas State University CVM-SMILE and the Kansas City Area Life Science Institute
文摘nPendred syndrome （PS） is characterized by autosomal recessive inheritance of goiter associated with a defect of iodide organification, hearing loss, enlargement of the vestibular aqueduct （EVA）, and mutations of the SLC26A4 gene. However, not all EVA patients have PS or SLC26A4 mutations. Two mutant alleles of SLC26A4 are detected in 1/4 of North American or European EVA populations, one mutant allele is detected in another 1/4 of patient populations, and no mutations are de-tected in the other 1/2. The presence of two mutant al-leles of SLC26A4 is associated with abnormal iodide or-ganification, increased thyroid gland volume, increased severity of hearing loss, and bilateral EVA. The pres-ence of a single mutant allele of SLC26A4 is associated with normal iodide organification, normal thyroid gland volume, less severe hearing loss and either bilateral or unilateral EVA. When other underlying correlations are accounted for, the presence of a cochlear malformation or the size of EVA does not have an effect on hearing thresholds. This is consistent with observations of an Slc26a4 mutant mouse model of EVA in which hearing loss is independent of endolymphatic hydrops or in-ner ear malformations. Segregation analyses of EVA in families suggest that the patients carrying one mutant allele of SLC26A4 have a second, undetected mutant allele of SLC26A4, and the probability of a sibling hav-ing EVA is consistent with its segregation as an autoso-mal recessive trait. Patients without any mutations are an etiologically heterogeneous group in which siblings have a lower probability of having EVA. SLC26A4 muta-tion testing can provide prognostic information to guide clinical surveillance and management, as well as the probability of EVA affecting a sibling.
