Severe bleeding complications and multiple kidney transplants in a patient with tuberous sclerosis complex caused by a novel TSC2 missense variant

摘要

We presented an extremely severe case of tuberous sclerosiscomplex (TSC) in a female patient with recurring, lifethreateningbleeding complications related to renal angiomyolipomas.Massive intratumoral hemorrhage requiredsurgical removal of both angiomyolipomatous kidneysand kidney transplantation. During the follow-up period,the patient developed severe metrorrhagia that eventuallyled to hysterectomy and salpingo-oophorectomy. Bleedingfrom the operative sites caused the loss of the first kidneytransplant received from the mother, and immediatehemorrhagic shock led to the loss of the second, cadaverickidney allograft. The third kidney transplant had a successfuloutcome. Pathological analysis of all tissue specimensshowed TSC-associated lesions and deformed blood vesselsin the surgically removed organs. Molecular geneticanalysis of TSC1 and TSC2 in the DNA of peripheral leukocytesidentified a novel TSC2 c.3599GC (p.R1200P) variant.Functional assessment confirmed the likely pathogenicityof the TSC2 c.3599GC (p.R1200P) variant. To the best ofour knowledge, this is the first report of the c.3599GC(p.R1200P) variant in exon 29 of the TSC2 gene related to asevere clinical course and multiple kidney transplants in apatient with TSC.