Doroftei Bogdan, Maftei Radu, Ilie Ovidiu-Dumitru, Armeanu Theodora, Puiu Maria, Ivanov Iuliu, Nemtanu Loredana
Department of Mother and Child Medicine, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", University Street, No. 16, 700115 Iasi, Romania.
Clinical Hospital of Obstetrics and Gynecology "Cuza Voda", Cuza Voda Street, No. 34, 700038 Iasi, Romania.
Diagnostics (Basel). 2021 Dec 10;11(12):2328. doi: 10.3390/diagnostics11122328.
Severe congenital myopathy with fatal cardiomyopathy (EOMFC) is a rare genetic neuromuscular disorder inherited in an autosomal recessive manner. Here we presented a successful pregnancy obtained by in vitro fertilization (IVF) using preimplantation genetic testing (PGT) in one young Romanian carrier couple that already lost mutation(s) within the TNN gene and whose first baby passed away due to multiple complications. It was delivered via emergency C-section at 36 weeks and fully dependent on artificial ventilation for a couple of months, weighing 2200 g and an APGAR score of 3. The aCGH + SNP analysis revealed an abnormal profile of the first newborn; three areas associated with loss of heterozygosity on chromosome 1 (q25.1-q25.3) of 6115 kb, 5 (p15.2-p15.1) of 2589 kb and 8 (q11.21-q11.23) of 4830 kb, a duplication of 1104 kb on chromosome 10 in the position q11.22, and duplication of 1193 kb on chromosome 16 in the position p11.2p11.1. Subsequently, we proceeded to test the parents and showed that both parents are carriers; confirmed by Sanger and NGS sequencing-father-on Chr2(GRCh37):g.179396832_179396833del-TTN variant c.104509_104510del p.(Leu34837Glufs12)-exon 358 and mother-on Chr2(GRCh37):g.179479653G>C-TTN variant c.48681C>G p.(Tyr16227)-exon 260. Their first child died shortly after birth due to multiple organ failures, possessing both parent's mutations; weighing 2200 g at birth and received an APGAR score of 3 following premature delivery via emergency C-section at 36 weeks. Two embryos were obtained following the IVF protocol; one possessed the mother's mutation, and the other had no mutations and was normal (WT). In contrast with the first birth, the second one was uneventful. A healthy female baby weighing 2990 g was delivered by C-section at 38 weeks, receiving an APGAR score of 9.
伴有致命性心肌病的严重先天性肌病（EOMFC）是一种罕见的常染色体隐性遗传的神经肌肉疾病。在此，我们介绍了一对年轻的罗马尼亚携带者夫妇通过体外受精（IVF）并使用植入前基因检测（PGT）成功受孕的案例。这对夫妇已经在TNN基因内发生了突变，并且他们的第一个孩子因多种并发症而夭折。第二个孩子在36周时通过紧急剖宫产出生，体重2200克，阿氏评分3分，出生后几个月完全依赖人工通气。对第一个新生儿的aCGH + SNP分析显示其基因图谱异常；在1号染色体（q25.1 - q25.3）上有6115 kb的三个与杂合性缺失相关的区域，5号染色体（p15.2 - p15.1）上有2589 kb的区域，8号染色体（q11.21 - q11.23）上有4830 kb的区域，10号染色体在q11.22位置有1104 kb的重复，16号染色体在p11.2p11.1位置有1193 kb的重复。随后，我们对父母进行检测，结果显示父母双方均为携带者；通过桑格测序和二代测序（NGS）确认——父亲在Chr2（GRCh37）：g.179396832_179396833del - TTN变异体c.104509_104510del p.(Leu34837Glufs12)——外显子358，母亲在Chr2（GRCh37）：g.179479653G>C - TTN变异体c.48681C>G p.(Tyr16227)——外显子260。他们的第一个孩子出生后不久因多器官功能衰竭死亡，携带了父母双方的突变；出生时体重2200克，在36周时通过紧急剖宫产早产，阿氏评分3分。按照IVF方案获得了两个胚胎；一个携带母亲的突变，另一个没有突变，是正常的（野生型）。与第一次分娩不同，第二次分娩过程顺利。一个健康的女婴在38周时通过剖宫产出生，体重2990克，阿氏评分9分。
