title: Two common and three novel PDS mutations in Thai patients with Pendred syndrome.
abstract: Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the PDS gene. Most published mutation studies of Pendred syndrome have dealt with Western populations. In this study, we examined clinical and molecular characteristics of 16 affected individuals in 6 unrelated Thai families. Of all the affected, 100% (16/16) had bilateral deafness, 68.8% (11/16) goiters, and 25% (4/16) hypothyroidism. Follicular thyroid carcinoma and Hürthle cell adenoma were found in affected members of a family, raising the possibility of an increased risk of thyroid carcinoma in Pendred syndrome patients. Sequence analysis of the entire coding region of the PDS gene successfully identified all 12 mutant alleles in these 6 families. The 12 identified mutant alleles constituted 6 distinct mutations including 3 splice site mutations (IVS4-1G>A, IVS7-2A>G, IVS9- 1G>A), one frame shift mutation (1548insC) and 2 missense mutations (T67S, H723R). Eight mutations out of 12 were constituted by IVS7- 2A>G and 1548insC, each one being present in 4 distinct alleles in our studied group. The identification of these two frequent PDS mutations will facilitate the molecular diagnosis of Pendred syndrome in Thai populations. In addition, three newly identified mutations, T67S, IVS4-1G>A, and IVS9-1G>A, were not observed in 50 unrelated healthy Thai controls.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. thiti.s@chula.ac.th
authors.forename: T
authors.initials: T
authors.lastname: Snabboon
authors.forename: W
authors.initials: W
authors.lastname: Plengpanich
authors.forename: S
authors.initials: S
authors.lastname: Saengpanich
authors.forename: S
authors.initials: S
authors.lastname: Sirisalipoch
authors.forename: S
authors.initials: S
authors.lastname: Keelawat
authors.forename: S
authors.initials: S
authors.lastname: Sunthornyothin
authors.forename: W
authors.initials: W
authors.lastname: Khovidhunkit
authors.forename: S
authors.initials: S
authors.lastname: Suwanwalaikorn
authors.forename: V
authors.initials: V
authors.lastname: Sridama
authors.forename: V
authors.initials: V
authors.lastname: Shotelersuk
mesh_terms: D018249:Adenoma, Oxyphilic / Q000235:genetics; D000328:Adult; D000483:Alleles; D003638:Deafness / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006042:Goiter / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007037:Hypothyroidism / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D007454:Iodides / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D012307:Risk Factors; D000076988:Sulfate Transporters; D013577:Syndrome; D013785:Thailand; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: D007454:Iodides; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters