Genotype And Phenotypic Characteristics Of Pseudohypoparathyroidism And The Relationship With IPPSD

Objective: To analyze the clinical characteristics and Genetic results of 5patients and their families with pseudohypoparathyroidism and to improve diagnosis and treatment of pseudohypoparathyroidism.Methods: This is a Retrospective analysis.The clinical manifestations and laboratory examination of the patients who were admitted to the Department of Pediatrics,the Second Hospital of Hebei Medical University from 2015 to 2020 were analyzed and summarized.Medical exon gene testing was performed by the patients and their family members for further genetic diagnosis,and reviewed the relevant literature.Results: The five patients were confirmed with PHP according to the clinical data and genetic tests,among them 2 cases for half-sisters.The patients were hospitalized with skin nodules,tetany,congenital hypothyroidism,short stature or Intermittent convulsions,but there are different degrees of AHO phenotype,associated with elevated TSH,some with elevated PTH,so they were diagnosed clinically as PHP.Genetic testing found that cases 1 to 4 carried GNAS gene mutations,which could be confirmed as pseudohypoparathyroidism.Case 5 refused genetic testing.According to the newly proposed Inactivating PTH/PTHr P Signaling Disorders(IPPSD),the five subjects were diagnosed with i PPSD2:PHP-Ia/PHP-Ic.Three mutations located in exon 1,6 and 12 of GNAS gene were found,which were termination mutation,frameshift mutation and missense mutation.Among them,the missense mutation C.1027C>G(p.R343G)was a new mutation that has not been reported yet.Conclusion: The 4 patients were diagnosed as PHP by clinical examination and GNAS gene testing,two of whom were half-sisters,which was rarely reported,and the missense mutation of GNAS gene C.1027C>G(p.R343G)in this study was reported for the first time in the world.The onset of PHP could happen at an early age,and the clinical manifestations are heterogeneous,so the delayed diagnosis is frequent because of the atypical early symptoms,which could cause adverse effect to the patient and family.For those with endocrine hormone resistance and AHO phenotype,GNAS gene testing should be performed in time to further confirm the diagnosis and guide the reproduction.