Abstract：
To report two novel TTN variants associated with fetal recessive titinopathy, thereby broadening the range of TTN variants that can lead to titinopathy. Clinical information on the fetus and parents was gathered, and genomic DNAs were extracted from the fetal tissue and family members\' peripheral blood samples. Exome sequencing on fetal DNA was performed and following bioinformatics analysis, the suspected pathogenic variants were confirmed through Sanger sequencing. Prenatal ultrasound performed at 29 weeks of gestation revealed hydrops fetalis, decreased fetal movements, multiple joint contractures and polyhydramnios. Intrauterine fetal death was noted in the third trimester. Exome sequencing revealed compound heterozygous variants in the TTN gene: a paternally inherited allele c.101227C>T (p.Arg33743Ter) and a maternally inherited c.104254C>T (p.Gln34752Ter) allele. These variants have not been previously reported and are evaluated to be likely pathogenic according to the American College of Medical Genetics and Genomics guidelines. We report a fetus with hydrops fetalis and arthrogryposis multiplex congenita associated with a compound heterozygote in the TTN gene. Our report broadens the clinical and genetic spectrum associated with the TTN-related conditions.
摘要：
报告与胎儿隐性肌动蛋白病相关的两种新的TTN变异，从而扩大可导致肌动蛋白病的TTN变体的范围。收集了胎儿和父母的临床信息，从胎儿组织和家族成员外周血样本中提取基因组DNA。对胎儿DNA进行外显子组测序，并进行生物信息学分析，通过Sanger测序确认了疑似致病变异.妊娠29周时进行的产前超声检查显示胎儿水肿，胎动减少,多发关节挛缩和羊水过多。在妊娠晚期发现了宫内胎儿死亡。外显子组测序揭示了TTN基因中的复合杂合变体：父系遗传的等位基因c.101227C>T（p。Arg33743Ter）和母系遗传c.104254C>T（p。Gln34752Ter)等位基因。这些变异以前没有报道过，根据美国医学遗传学和基因组学学会指南，这些变异被评估为可能致病。我们报告了一个胎儿，胎儿水肿和多发性先天性关节炎与TTN基因中的复合杂合子相关。我们的报告拓宽了与TTN相关疾病相关的临床和遗传谱。
