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

Abstract

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.