Kawamura Hiroshi, Ikawa Masamichi, Hirono Keiichi, Kimura Junya, Okuno Takashi, Kawatani Masao, Inai Kunihiro, Hata Yukiko, Nishida Naoki, Yoshida Yoshio
Department of Obstetrics and Gynecology, University of Fukui, Fukui, Japan.
Department of Medical Genetics, University of Fukui Hospital, Fukui, Japan.
Front Pediatr. 2023 Jun 8;11:1195222. doi: 10.3389/fped.2023.1195222. eCollection 2023.
Left ventricular noncompaction (LVNC) is a rare inherited cardiomyopathy with a broad phenotypic spectrum. The genotype-phenotype correlations in fetal-onset LVNC have not yet been fully elucidated. In this report, we present the first case of severe fetal-onset LVNC caused by maternal low-frequency somatic mosaicism of the novel myosin heavy chain 7 (MYH7) mutation.
A 35-year-old pregnant Japanese woman, gravida 4, para 2, with no significant medical or family history of genetic disorders, presented to our hospital. In her previous pregnancy at 33 years of age, she delivered a male neonate at 30 weeks of gestation with cardiogenic hydrops fetalis. Fetal echocardiography confirmed LVNC prenatally. The neonate died shortly after birth. In the current pregnancy, she again delivered a male neonate with cardiogenic hydrops fetalis caused by LVNC at 32 weeks of gestation. The neonate died shortly after birth. Genetic screening of cardiac disorder-related genes by next-generation sequencing (NGS) was performed which revealed a novel heterozygous missense MYH7 variant, NM_000257.3: c.2729A > T, p.Lys910Ile. After targeted and deep sequencing by NGS, the same MYH7 variant (NM_000257.3: c.2729A > T, p.Lys910Ile) was detected in 6% of the variant allele fraction in the maternal sequence but not in the paternal sequence. The MYH7 variant was not detected by conventional direct sequencing (Sanger sequencing) in either parent.
This case demonstrates that maternal low-frequency somatic mosaicism of an MYH7 mutation can cause fetal-onset severe LVNC in the offspring. To differentiate hereditary MYH7 mutations from MYH7 mutations, parental targeted and deep sequencing by NGS should be considered in addition to Sanger sequencing.
左心室心肌致密化不全（LVNC）是一种罕见的遗传性心肌病，具有广泛的表型谱。胎儿期发病的LVNC的基因型-表型相关性尚未完全阐明。在本报告中，我们展示了首例由母亲新型肌球蛋白重链7（MYH7）突变的低频体细胞嵌合引起的严重胎儿期LVNC病例。
一名35岁的日本孕妇，孕4产2，无重大遗传疾病病史或家族史，前来我院就诊。她33岁时的前次妊娠中，在妊娠30周时分娩了一名患有心源性胎儿水肿的男婴。胎儿超声心动图产前确诊为LVNC。该新生儿出生后不久死亡。在本次妊娠中，她在妊娠32周时再次分娩了一名因LVNC导致心源性胎儿水肿的男婴。该新生儿出生后不久死亡。通过下一代测序（NGS）对心脏疾病相关基因进行遗传筛查，发现了一个新的杂合错义MYH7变异，NM_000257.3:c.2729A>T，p.Lys910Ile。经NGS靶向深度测序后，在母亲序列中检测到相同的MYH7变异（NM_000257.3:c.2729A>T，p.Lys910Ile），变异等位基因比例为6%，而父亲序列中未检测到。父母双方的常规直接测序（桑格测序）均未检测到MYH7变异。
本病例表明，MYH7突变导致的母亲低频体细胞嵌合可导致后代胎儿期严重LVNC。为了区分遗传性MYH7突变和MYH7突变，除了桑格测序外，还应考虑对父母进行NGS靶向深度测序。
