He Shunzhi, Lv Na, Bao Hongchu, Wang Xiong, Li Jing
Reproductive Medicine Center, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, P.R. China.
Department of Prenatal Diagnosis, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, P.R. China.
BMC Med Genet. 2020 Sep 11;21(1):180. doi: 10.1186/s12881-020-01120-z.
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.
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.
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.
结节性硬化症（TSC）是一种常染色体显性遗传病，其特征为多器官系统出现错构瘤，包括脑、皮肤、心脏、肾脏和肺。从基因角度来看，TSC是由TSC1或TSC2基因的致病性变异引起的。
我们报告了一例32岁汉族男性散发性TSC病例，其配偶有两次自然流产史，并有一次人工流产史，此次人工流产的30周胎儿经超声检查发现患有心脏横纹肌瘤。通过下一代测序在男性患者及其流产胎儿中鉴定出TSC2基因中的一种新型杂合错义变异（外显子35：c.4511T>C：p.L1504P），但在其妻子或其父母双方中未发现。根据美国医学遗传学与基因组学学会（ACMG）/美国分子病理学会（AMP）标准，该变异被分类为“可能致病”变异。
鉴定出的新型TSC2：c.4511T>C变异极有可能与TSC相关，并可能导致不良生殖结局。建议该患者未来进行体外受精-胚胎移植（IVF-ET）及TSC的植入前基因诊断，以预防胎儿患TSC。
