Prenatal diagnosis identifies compound heterozygous variants in RYR1 that causes ultrasound abnormalities in a fetus
Abstract Objective We presented a non-consanguineous healthy Chinese couple with five pregnancies, three early miscarriages, the fetus II-2 and II-5 with similar abnormal phenotypes of fetal hydrops, scoliosis, fetal akinesia and polyhydramnios. This study aimed to uncover the molecular etiology of...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-022-01358-x |
| _version_ | 1811208810613702656 |
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| author | Qiuling Zhao Xiaoduo Li Li Liu Xu Zhang Xin Pan Hong Yao Yongyi Ma Bo Tan |
| author_facet | Qiuling Zhao Xiaoduo Li Li Liu Xu Zhang Xin Pan Hong Yao Yongyi Ma Bo Tan |
| author_sort | Qiuling Zhao |
| collection | DOAJ |
| description | Abstract Objective We presented a non-consanguineous healthy Chinese couple with five pregnancies, three early miscarriages, the fetus II-2 and II-5 with similar abnormal phenotypes of fetal hydrops, scoliosis, fetal akinesia and polyhydramnios. This study aimed to uncover the molecular etiology of this family with a history of multiple adverse pregnancies. Materials and methods DNA extracted from the fifth fetal umbilical cord and parents’ peripheral blood were subjected to SNP-array and whole exome sequencing. The result was verified by Sanger sequencing. Functional characterization of the c.2682G > C (p.Ile860_Pro894del) variant was completed by minigene splicing assay. Results Trio whole-exome sequencing has identified compound heterozygous variants in RYR1 (c.2682G > C; p.Ile860_Pro894del and c.12572G > A; p.Arg4191His) in fetus II-5. The variant c.2682G > C (p.Ile860_Pro894del) comes from the father and the c.12572G > A (p.Arg4191His) comes from the mother. The c.2682G > C (p.Ile860_Pro894del) affects the splice site resulting in exon 21 skipping, therefore is classified as likely pathogenic. The c.12572G > A (p.Arg4191His) locates in the C-terminal hot spots region of the RYR1, classified as of uncertain significance. Conclusions We report the first prenatal case of RYR1-related disorders in Chinese population, expanding the variant spectrum of RYR1 in fetuses. |
| first_indexed | 2024-04-12T04:29:14Z |
| format | Article |
| id | doaj.art-88785578a6d448738be1e5cb3ed6181c |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-04-12T04:29:14Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-88785578a6d448738be1e5cb3ed6181c2022-12-22T03:48:00ZengBMCBMC Medical Genomics1755-87942022-09-011511710.1186/s12920-022-01358-xPrenatal diagnosis identifies compound heterozygous variants in RYR1 that causes ultrasound abnormalities in a fetusQiuling Zhao0Xiaoduo Li1Li Liu2Xu Zhang3Xin Pan4Hong Yao5Yongyi Ma6Bo Tan7Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical UniversityQijiang Maternal and Child Health HospitalDepartment of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Gynecology and Obstetrics, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical UniversityAbstract Objective We presented a non-consanguineous healthy Chinese couple with five pregnancies, three early miscarriages, the fetus II-2 and II-5 with similar abnormal phenotypes of fetal hydrops, scoliosis, fetal akinesia and polyhydramnios. This study aimed to uncover the molecular etiology of this family with a history of multiple adverse pregnancies. Materials and methods DNA extracted from the fifth fetal umbilical cord and parents’ peripheral blood were subjected to SNP-array and whole exome sequencing. The result was verified by Sanger sequencing. Functional characterization of the c.2682G > C (p.Ile860_Pro894del) variant was completed by minigene splicing assay. Results Trio whole-exome sequencing has identified compound heterozygous variants in RYR1 (c.2682G > C; p.Ile860_Pro894del and c.12572G > A; p.Arg4191His) in fetus II-5. The variant c.2682G > C (p.Ile860_Pro894del) comes from the father and the c.12572G > A (p.Arg4191His) comes from the mother. The c.2682G > C (p.Ile860_Pro894del) affects the splice site resulting in exon 21 skipping, therefore is classified as likely pathogenic. The c.12572G > A (p.Arg4191His) locates in the C-terminal hot spots region of the RYR1, classified as of uncertain significance. Conclusions We report the first prenatal case of RYR1-related disorders in Chinese population, expanding the variant spectrum of RYR1 in fetuses.https://doi.org/10.1186/s12920-022-01358-xRyanodine receptor type 1 geneRYR1-related disordersUltrasound abnormalitiesSplice-site variantWhole-exome sequencing |
| spellingShingle | Qiuling Zhao Xiaoduo Li Li Liu Xu Zhang Xin Pan Hong Yao Yongyi Ma Bo Tan Prenatal diagnosis identifies compound heterozygous variants in RYR1 that causes ultrasound abnormalities in a fetus BMC Medical Genomics Ryanodine receptor type 1 gene RYR1-related disorders Ultrasound abnormalities Splice-site variant Whole-exome sequencing |
| title | Prenatal diagnosis identifies compound heterozygous variants in RYR1 that causes ultrasound abnormalities in a fetus |
| title_full | Prenatal diagnosis identifies compound heterozygous variants in RYR1 that causes ultrasound abnormalities in a fetus |
| title_fullStr | Prenatal diagnosis identifies compound heterozygous variants in RYR1 that causes ultrasound abnormalities in a fetus |
| title_full_unstemmed | Prenatal diagnosis identifies compound heterozygous variants in RYR1 that causes ultrasound abnormalities in a fetus |
| title_short | Prenatal diagnosis identifies compound heterozygous variants in RYR1 that causes ultrasound abnormalities in a fetus |
| title_sort | prenatal diagnosis identifies compound heterozygous variants in ryr1 that causes ultrasound abnormalities in a fetus |
| topic | Ryanodine receptor type 1 gene RYR1-related disorders Ultrasound abnormalities Splice-site variant Whole-exome sequencing |
| url | https://doi.org/10.1186/s12920-022-01358-x |
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