Triple repeated fetal congenital heart disease linked to PLD1 mutation: a case report

Journal of Medical Case Reports

Case Report

Nobuhiko Okamoto¹  Daisuke Fujita²  Hiroshi Maruoka²  Masae Yoo²  Sosuke Hashida²  Satoe Fujiwara²  Misa Nunode²  Natsuko Morita²  Masahide Ohmichi²  Ruri Nishie²  Takumi Sano²  Yoko Nagayasu²  Atsushi Daimon²  Hikaru Murakami²  Yuki Masuda³  Yutaka Odanaka⁴ 

[1] Department of Medical Genetics, Osaka Women’s and Children’s Hospital, Izumi, Japan;Department of Obstetrics and Gynecology, Osaka Medical and Pharmaceutical University, Takatsuki, Japan;Department of Obstetrics and Gynecology, Osaka Medical and Pharmaceutical University, Takatsuki, Japan;Department of Obstetrics and Gynecology, Saiseikai Suita Hospital, Suita, Japan;Department of Pediatrics, Osaka Medical and Pharmaceutical University, Takatsuki, Japan;

关键词: Congenital heart disease;    Cardiology;    Genetic;    Genetic disease;    PLD1;   

DOI  :  10.1186/s13256-023-04149-9

 received in 2023-05-09, accepted in 2023-08-28,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCongenital heart disease occurs in approximately 1 in 100 cases. Although sibling occurrence is high (3–9%), the causative genes for this disease are still being elucidated. PLD1 (Phospholipase D1) is a recently discovered gene; however, few case reports have been published on it. In this report, we describe a case of triplicate fetal congenital heart disease that was diagnosed as a PDL1 mutation. Our objective is to explore the clinical manifestations of PLD1 mutations in this particular case.Case presentationA 32-year-old Japanese woman (gravida, para 0) was introduced since fetus four chamber view was not clear and was diagnosed with ductus arteriosus-dependent left ventricular single ventricle and pulmonary atresia at 21 weeks and 1 day of gestation during her first pregnancy. Artificial abortion using Gemeprost was performed at 21 weeks and 5 days of gestation. The second pregnancy was diagnosed as pulmonary atresia with intact ventricular septum with cardiomegaly, a cardiothoracic area ratio of more than 35%, and a circulatory shunt at 13 weeks and 3 days of gestation. Subsequently, intrauterine fetal death was confirmed at 14 weeks and 3 days of gestation. Regarding the third pregnancy, fetal ultrasonography at 11 weeks and 5 days of gestation showed mild fetal hydrops and moderate tricuspid valve regurgitation. At 16 weeks and 5 days of gestation, the fetus was suspected to have a left ventricular-type single ventricle, trace right ventricle, pulmonary atresia with intact ventricular septum, or cardiomyopathy. Cardiac function gradually declined at 26 weeks of gestation, and intrauterine fetal death was confirmed at 27 weeks and 5 days of gestation. The fourth pregnancy resulted in a normal heart with good progression and no abnormal baby. We submitted the first and second fetuses’ umbilical cord, third fetus’ placenta, and the fourth fetus’ blood to genetic testing using whole exome analysis with next generation sequencing. Genetic analysis identified hemizygous PLD1 mutations in the first, second, and third fetuses. The fourth fetus was heterozygous. In addition, the parents were heterozygous for PLD1. This case is based on three consecutive cases of homozygosity for the PLD1 gene in the sibling cases and the fetuses with recurrent right ventricular valve dysplasia. This will elucidate the cause of recurrent congenital heart disease and intrauterine fetal death and may serve as an indicator for screening the next fetus. To date, homozygous mutations in PLD1 that repeat three times in a row are not reported, only up to two times. The novelty of this report is that it was repeated three times, followed by a heterozygous live birth.ConclusionsThis report is consistent with previous reports that mutations in PLD1 cause right ventricular valve dysplasia. However, there have been few case reports of PLD1 mutations, and we hope that this report will contribute to elucidate the causes of congenital heart disease, especially right ventricular valve dysplasia, and that the accumulation of such information will provide more detailed information on PLD1 mutations in heart disease.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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Fig. 3