关键词: 家族性低镁血症伴高钙尿症和肾钙沉着症, 原发性高草酸尿症Ⅰ型, CLDN16基因, AGXT基因

Abstract: Ｏｂｊｅｃｔｉｖｅ：To knowledge about the phenotype of hereditary nephrolithiasis and to further improve the recognition of this disorder.
Ｍｅｔｈｏｄｏｌｏｇｙ：Retrospectively analyzed the clinical data of two patients with hereditary nephrolithiasis.The causative genes were analyzed using targeted next generation sequencing and Sanger sequencing.
Ｒｅｓｕｌｔｓ：Case 1,a Han ethnicity male.Multiple renal stones were found at one year old.Cystolithotomy and extracorporeal shock wave lithotripsy were carried out when he was two and six years old,respectively.At the age of 20,he progressed to end stage renal disease with serum magnesium 056 mmol/L.Bilateral small kidneys with multiple stones were showed by CT.A homozygous nonsense mutation in exon 4 (c715G>T,pGly239*) of CLDN16 was identified in this patient,which could be traced to both of his parents.We diagnosed this patient as familial hypomagnesemia with hypercalciuria and nephrocalcinosis based on clinical manifestations and genetic testing result. Case 2,a Han ethnicity female. Yellow and white kidney stones were excreted when she was one year old. At the age of 78,Xray showed bilateral kidney stones more than once. Stone composition analysis suggested “calcium oxalate”. At the age of 22,she developed to end stage renal disease and was treated with hemodialysis,ultrasound indicated bilateral small kidneys with multiple stones. She had a family history of renal stone. Compound heterozygous mutations in exons 1 (c32C>G,pPro11Arg) and 2 (c346G>A,pGly116Arg) of AGXT were detected in this patient,which were inherited from her father and mother,respectively. We diagnosed this patient as primary hyperoxaluria type 1 based on clinical presentations and genetic testing result.
Ｃｏｎｃｌｕｓｉｏｎ：Genetic factors should be considered in children with recurrent nephrolithiasis. Stone composition analysis and genetic testing can help diagnose and guide treatment as early as possible.

Key words: familial hypomagnesemia with hypercalciuria and nephrocalcinosis, primary hyperoxaluria type 1, CLDN16, AGXT