Gene Mutations in Chronic Kidney Disease Patients With Secondary Hyperparathyroidism and Sagliker Syndrome

DEMİRHAN O., Arslan A., Sagliker Y., Akbal E., Ergun S., Bayraktar R., ...More

JOURNAL OF RENAL NUTRITION, vol.25, no.2, pp.176-186, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 25 Issue: 2
  • Publication Date: 2015
  • Doi Number: 10.1053/j.jrn.2014.12.008
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.176-186
  • Çukurova University Affiliated: Yes


Sagliker syndrome (SS) develops particularly before pubertywhile 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 inGNAS1were 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 introngenicmutations (introns 65626, 70387, 70817). Wefound 10mutationswith differentmanner in FGF23 gene. Two were defined previously but remaining 8 were novel mutations. Threewere in intronic region near exon 2. We sequenced all exons and intronic regions near exon-exon junction regions ofFGFR3gene. Wefound 22mutations with differentmanner. Sixweredefinedpreviously 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 asMcCune-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. (C) 2015 by the National Kidney Foundation, Inc. All rights reserved.