title: Gene mutations in chronic kidney disease patients with secondary hyperparathyroidism and Sagliker syndrome.
abstract: Sagliker syndrome (SS) develops particularly before puberty while chronic kidney disease (CKD) reaches stage 3 with overt secondary hyperparathyroidism. We conducted screening for mutations in all the 13 exons of GNAS1 gene, all 3 exons of FGF23, and all 18 exons in FGFR3 genes in 23 patients. In 73.9% (17 of 23) patients, 17 genetic abnormalities in GNAS1 were detected. Seven (58.3%) of 12 nucleotide alterations comprised novel missense mutations and 3 nonsense. Mismutations were in different manner. There were also 6 heterozygous transversion polymorphisms in exons. Six were introngenic mutations (introns 65626, 70387, 70817). We found 10 mutations with different manner in FGF23 gene. Two were defined previously but remaining 8 were novel mutations. Three were in intronic region near exon 2. We sequenced all exons and intronic regions near exon-exon junction regions of FGFR3 gene. We found 22 mutations with different manner. Six were defined previously and remaining 16 were novel mutations. Eight of them were in intronic region near exon 11 and the last 2 were in noncoding exonic region of exons. One was in the exon-exon junction region between exon 11 and 12, therefore this mutation might be preventing splicing of this intron. Because the incidence of CKD late stage 3 is around 8% but the incidence of SS is around 0.5% in CKD, these gene mismutations might be responsible for bone deformities such as McCune-Albright syndrome and achondroplasias. Although our patients were not resembling any of them, they could be in between, and SS might be a combination-compulsion of bone dysplasias-hereditary osteodystrophies and CKD.
authors.affiliation: Cukurova University, Adana, Turkey.
authors.forename: Osman
authors.initials: O
authors.lastname: Demirhan
authors.affiliation: Gaziantep University, Gaziantep, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Arslan
authors.affiliation: Sagliker Hypertension and Nephrology Unit, Adana, Turkey. Electronic address: ysagliker@yahoo.com.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Sagliker
authors.affiliation: Cukurova University, Adana, Turkey.
authors.forename: Eylul
authors.initials: E
authors.lastname: Akbal
authors.affiliation: Gaziantep University, Gaziantep, Turkey.
authors.forename: Sercan
authors.initials: S
authors.lastname: Ergun
authors.affiliation: Gaziantep University, Gaziantep, Turkey.
authors.forename: Recep
authors.initials: R
authors.lastname: Bayraktar
authors.affiliation: Sutcu Imam University, Kahramanmaras, Turkey.
authors.forename: Hasan Sabit
authors.initials: HS
authors.lastname: Sagliker
authors.affiliation: Sutcu Imam University, Kahramanmaras, Turkey.
authors.forename: Ekrem
authors.initials: E
authors.lastname: Dogan
authors.affiliation: Sutcu Imam University, Kahramanmaras, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Gunesacar
authors.affiliation: Baskent University, Adana, Turkey.
authors.forename: Piril Sagliker
authors.initials: PS
authors.lastname: Ozkaynak
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D019465:Craniofacial Abnormalities / Q000235:genetics*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D051436:Renal Insufficiency, Chronic / Q000235:genetics*; D013577:Syndrome