A novel TSC2 c.4511 T > C missense variant associated with tuberous sclerosis complex
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CASE REPORT
Open Access
A novel TSC2 c.4511 T > C missense variant associated with tuberous sclerosis complex Shunzhi He1†, Na Lv2†, Hongchu Bao1, Xiong Wang1 and Jing Li3*
Abstract Background: Tuberous sclerosis complex (TSC) is an autosomal-dominant hereditary disease characterized by hamartomas of multiple organ systems, including the brain, skin, heart, kidney and lung. Genetically, TSC is caused by pathogenic variants in the TSC1 or TSC2 gene. Case presentation: We reported a sporadic case of a 32-year-old Han Chinese male diagnosed with TSC, whose spouse had a history of two spontaneous miscarriages and an induced abortion of a 30-week fetus identified with cardiac rhabdomyoma by ultrasound. A novel heterozygous missense variant in the TSC2 gene (Exon35:c.4511 T > C: p.L1504P) was identified in the male patient and the aborted fetus by next-generation sequencing, but not in his wife or both his parents. According to the ACMG/AMP criteria, this variant was classified as a “likely pathogenic” variant. Conclusion: The novel TSC2:c.4511 T > C variant identified was highly likely associated with TSC and could potentially lead to adverse reproductive outcomes. IVF-ET and pre-implantation genetic diagnosis for TSC are recommended for this patient in the future to prevent fetal TSC. Keywords: Tuberous sclerosis complex, TSC1, TSC2, Novel variant, Next generation sequencing, Preimplantation genetic testing
Background Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disease that is characterized by hamartomas of multiple organ systems, including the brain, skin, heart, kidney and lung. Symptoms of the central nervous system include epilepsy, learning disabilities, behavioural problems, and autism. Additionally, 70–80% of TSC patients develop kidney manifestations, usually angiomyolipoma and renal cysts. Genetically, TSC is caused by pathogenic variants in the TSC1 or TSC2 gene [1], accounting for approximately 10–30% and nearly 70% of all cases respectively [2]. Variants in TSC2 cause more severe * Correspondence: [email protected] † Shunzhi He and Na Lv contributed equally to this work. 3 Electrocardiogram Room, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China Full list of author information is available at the end of the article
symptoms [3]. In this study, we identified a novel de novo variant in TSC2 in a male TSC patient and his aborted 30week fetus with cardiac rhabdomyoma by ultrasonography, a typical symptom of fetal TSC.
Case presentation The patient (proband) was a 32-year-old male, who was admitted to our reproductive centre with a referral for “recurrent spontaneous miscarriage of his spouse”. He had a history of head injury at the age of 6 years old, accompanied by brief loss of consciousness, but no skull fracture or intracranial haemorrhage occurred. One year after, fibrous nodules gradually appeared on the tip of his nose, nasolabial groove, cheek and mandible. He started to experience recurring epilepsy more than 10 attacks
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