Mutational analysis of the GNAS1 gene in patients with chronic renal failure, secondary hyperparathyroidism and uglifying face appearances (Sagliker syndrome)

Sagliker syndrome (SS) seems to be related to chronic kidney disease (CKD), secondary hyperparathyroidism (SH) and uglifying face appearances. The etiology of SS is not known, and it is strongly thought that genetics may be the major factor in the etiology. The genetics importance of GNAS1 gene mutations on outcome in patients with SS is unclear, and no search has addressed GNAS1 mutations. Therefore, we conducted clinical and genetical studies including screening for mutations in the 13 exons of the GNAS1 gene in 23 subjects with SS. In 47.8% of the patients, 17 genetic abnormalities in GNAS1 were detected. Seven (58.3%) of 12 nucleotide alterations comprised novel missense mutations and three nonsense. Mismutations were in different manners. For 16 regions of the GNAS1 gene in which a missense and nonsense mutations, and heterozigot transversions (polymorphisms) were identified in 11 patients, and no mutated GNAS1 genomic in DNA of control subjects. There was nonsense mutations in 5 patients. Polymorphisms and other nonpathogenic mutations have been identified in 43.5% of the patients. There were also 6 heterozygous tranversion polymorphism in exons. Six were introngenic mutations. These results expand the spectrum of GNAS1 missense mutations associated with SS, and are consistent with an insufficiency of GNAS1 playing a role in the clinical phenotype of loss of function mutations and with a functional GNAS1 allele having a predominant role. At the same time, these findings may be helpful in conducting further molecular and biological studies on CKD, secondary hyperparathyroidism and uglifying face appearances.

синдром Сагликера, ген GNAS1, мутации, полиморфизм, хроническая болезнь почек, гиперпаратиреоз, обезображивание лица, Sagliker syndrome, GNAS1 gene, mutations, polymorphism, chronic kidney disease, hyperparathyroidism, uglifying face appearances

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