Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case report
BackgroundLeft 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...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1195222/full |
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| author | Hiroshi Kawamura Masamichi Ikawa Keiichi Hirono Junya Kimura Takashi Okuno Masao Kawatani Masao Kawatani Kunihiro Inai Yukiko Hata Naoki Nishida Yoshio Yoshida |
| author_facet | Hiroshi Kawamura Masamichi Ikawa Keiichi Hirono Junya Kimura Takashi Okuno Masao Kawatani Masao Kawatani Kunihiro Inai Yukiko Hata Naoki Nishida Yoshio Yoshida |
| author_sort | Hiroshi Kawamura |
| collection | DOAJ |
| description | BackgroundLeft 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.Case presentationA 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.ConclusionsThis 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 de novo MYH7 mutations, parental targeted and deep sequencing by NGS should be considered in addition to Sanger sequencing. |
| first_indexed | 2024-03-13T06:47:30Z |
| format | Article |
| id | doaj.art-906b3b58f7744e1198c679e0ae25c4f4 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-03-13T06:47:30Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-906b3b58f7744e1198c679e0ae25c4f42023-06-08T05:20:47ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-06-011110.3389/fped.2023.11952221195222Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case reportHiroshi Kawamura0Masamichi Ikawa1Keiichi Hirono2Junya Kimura3Takashi Okuno4Masao Kawatani5Masao Kawatani6Kunihiro Inai7Yukiko Hata8Naoki Nishida9Yoshio Yoshida10Department of Obstetrics and Gynecology, University of Fukui, Fukui, JapanDepartment of Medical Genetics, University of Fukui Hospital, Fukui, JapanDepartment of Pediatrics, University of Toyama, Toyama, JapanDivision of Diagnostic Pathology, Surgical Pathology, University of Fukui Hospital, Fukui, JapanDepartment of Pediatrics, University of Fukui, Fukui, JapanDepartment of Medical Genetics, University of Fukui Hospital, Fukui, JapanDepartment of Pediatrics, University of Fukui, Fukui, JapanDepartment of Molecular Pathology, University of Fukui, Fukui, JapanDepartment of Legal Medicine, Faculty of Medicine, University of Toyama, Toyama, JapanDepartment of Legal Medicine, Faculty of Medicine, University of Toyama, Toyama, JapanDepartment of Obstetrics and Gynecology, University of Fukui, Fukui, JapanBackgroundLeft 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.Case presentationA 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.ConclusionsThis 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 de novo MYH7 mutations, parental targeted and deep sequencing by NGS should be considered in addition to Sanger sequencing.https://www.frontiersin.org/articles/10.3389/fped.2023.1195222/fullleft ventricular noncompactionmyosin heavy chain 7next-generation sequencingmosaicism mutationcase report |
| spellingShingle | Hiroshi Kawamura Masamichi Ikawa Keiichi Hirono Junya Kimura Takashi Okuno Masao Kawatani Masao Kawatani Kunihiro Inai Yukiko Hata Naoki Nishida Yoshio Yoshida Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case report Frontiers in Pediatrics left ventricular noncompaction myosin heavy chain 7 next-generation sequencing mosaicism mutation case report |
| title | Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case report |
| title_full | Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case report |
| title_fullStr | Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case report |
| title_full_unstemmed | Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case report |
| title_short | Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case report |
| title_sort | low frequency maternal novel myh7 mosaicism mutation in recurrent fetal onset severe left ventricular noncompaction a case report |
| topic | left ventricular noncompaction myosin heavy chain 7 next-generation sequencing mosaicism mutation case report |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1195222/full |
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