The Preliminary Study Of Application Of NGS In The Diagnosis Of Cryptogenic Hypokalemia

Objective: To analyze the clinical data and next-generation sequencing of hypokalemia with unknown etiology,we will explore the etiology of hypokalemia and evaluate the application value of next-generation sequencing in the diagnosis of cryptogenic hypokalemia.Methods: Take the patients whose discharge diagnosis was hypokalemia as the research subjects,by analyzing medical history,family history,disease features,laboratory findings and imaging examinations,patients,who had an early age of onset(<35 years old),and / or havd a clear family history of hypokalemia and excluded cases of secondary hypokalemia due to various diseases,were selected.Next-generation sequencing technology(sub-whole exome sequencing)was used in these selected cases to find causative mutations.The function of these mutations were then analyzed by the online software.Results: In 2017,162 cases of hypokalemia were diagnosed and treated in endocrinology department,of which 114 cases were diagnosed as cryptogenic hypokalemia.4 cases fulfilled inclusion criteria were selected for next-generation sequencing.The results suggested that one of the cases could be diagnosed as Gitelman syndrome,carrying a heterozygous mutation L858 H which will lead to the encoded protein of SLC12A3 function reduced.One case could be diagnosed as distal tubule acidosis,carrying SLC4A1 gene heterozygous mutation R388 C which has never been reported in the literature.The software predicted the pathogenic effect of the mutation R388 C.The other two cases were found no clinically significant mutations.Conclusions: It still has difficulty in etiological diagnosis of hypokalemia in clinical.Cryptogenic hypokalaemia with young onset and a clear family history may be an atypical manifestation of some hereditary disease and are required further next-generation sequencing to achieve early diagnosis,make therapeutic schedule and take genetic counseling.However,the application of sub-whole exome sequencing in the diagnosis of hypokalaemia needs to be further improved.