Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese population
Abstract Background Miller syndrome is a rare type of postaxial acrofacial dysostosis caused by biallelic mutations in the DHODH gene, which is characterized mainly by craniofacial malformations of micrognathia, orofacial clefts, cup‐shaped ears, and malar hypoplasia, combined with postaxial limb de...
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| Format: | Article |
| Language: | English |
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Wiley
2023-07-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.2186 |
| _version_ | 1827903419258503168 |
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| author | Kai Yang Li‐Man Fu Xiao‐Yang Chu Jing Zhang Wen‐Qi Chen You‐Sheng Yan Yi‐Peng Wang Dong‐Liang Zhang Cheng‐Hong Yin Qing Guo |
| author_facet | Kai Yang Li‐Man Fu Xiao‐Yang Chu Jing Zhang Wen‐Qi Chen You‐Sheng Yan Yi‐Peng Wang Dong‐Liang Zhang Cheng‐Hong Yin Qing Guo |
| author_sort | Kai Yang |
| collection | DOAJ |
| description | Abstract Background Miller syndrome is a rare type of postaxial acrofacial dysostosis caused by biallelic mutations in the DHODH gene, which is characterized mainly by craniofacial malformations of micrognathia, orofacial clefts, cup‐shaped ears, and malar hypoplasia, combined with postaxial limb deformities like the absence of fifth digits. Methods In this study, a prenatal case with multiple orofacial‐limb abnormities was enrolled, and a thorough clinical and imaging examination was performed. Subsequently, genetic detection with karyotyping, chromosomal microarray analysis (CMA) and whole‐exome sequencing (WES) was carried out. In vitro splicing analysis was also conducted to clarify the impact of one novel variant. Results The affected fetus displayed typical manifestations of Miller syndrome, and WES identified a diagnostic compound heterozygous variation in DHODH, consisting of two variants: exon(1‐3)del and c.819 + 5G > A. We conducted a further in vitro validation with minigene system, and the result indicated that the c.819 + 5G > A variant would lead to an exon skipping in mRNA splicing. Conclusions These findings provided with the first exonic deletion and first splice site variant in DHODH, which expanded the mutation spectrum of Miller syndrome and offered reliable evidence for genetic counseling to the affected family. |
| first_indexed | 2024-03-13T00:12:09Z |
| format | Article |
| id | doaj.art-febe9e52bd1948dcb157e822212bc045 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-13T00:12:09Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
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| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-febe9e52bd1948dcb157e822212bc0452023-07-12T11:50:09ZengWileyMolecular Genetics & Genomic Medicine2324-92692023-07-01117n/an/a10.1002/mgg3.2186Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese populationKai Yang0Li‐Man Fu1Xiao‐Yang Chu2Jing Zhang3Wen‐Qi Chen4You‐Sheng Yan5Yi‐Peng Wang6Dong‐Liang Zhang7Cheng‐Hong Yin8Qing Guo9Prenatal Diagnostic Center, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital Capital Medical University Beijing ChinaUltrasonic Department, Shijiazhuang Obstetrics and Gynecology Hospital Key Laboratory of Maternal and Fetal Medicine of Hebei Province Shijiazhuang ChinaDepartment of Stomatology Fifth Medical Center of Chinese PLA General Hospital Beijing ChinaPrenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital Key Laboratory of Maternal and Fetal Medicine of Hebei Province Shijiazhuang ChinaPrenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital Key Laboratory of Maternal and Fetal Medicine of Hebei Province Shijiazhuang ChinaPrenatal Diagnostic Center, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital Capital Medical University Beijing ChinaPrenatal Diagnostic Center, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital Capital Medical University Beijing ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology Capital Medical University Beijing ChinaPrenatal Diagnostic Center, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital Capital Medical University Beijing ChinaPrenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital Key Laboratory of Maternal and Fetal Medicine of Hebei Province Shijiazhuang ChinaAbstract Background Miller syndrome is a rare type of postaxial acrofacial dysostosis caused by biallelic mutations in the DHODH gene, which is characterized mainly by craniofacial malformations of micrognathia, orofacial clefts, cup‐shaped ears, and malar hypoplasia, combined with postaxial limb deformities like the absence of fifth digits. Methods In this study, a prenatal case with multiple orofacial‐limb abnormities was enrolled, and a thorough clinical and imaging examination was performed. Subsequently, genetic detection with karyotyping, chromosomal microarray analysis (CMA) and whole‐exome sequencing (WES) was carried out. In vitro splicing analysis was also conducted to clarify the impact of one novel variant. Results The affected fetus displayed typical manifestations of Miller syndrome, and WES identified a diagnostic compound heterozygous variation in DHODH, consisting of two variants: exon(1‐3)del and c.819 + 5G > A. We conducted a further in vitro validation with minigene system, and the result indicated that the c.819 + 5G > A variant would lead to an exon skipping in mRNA splicing. Conclusions These findings provided with the first exonic deletion and first splice site variant in DHODH, which expanded the mutation spectrum of Miller syndrome and offered reliable evidence for genetic counseling to the affected family.https://doi.org/10.1002/mgg3.2186acrofacial dysostosisDHODH geneMiller syndromewhole exome sequencing |
| spellingShingle | Kai Yang Li‐Man Fu Xiao‐Yang Chu Jing Zhang Wen‐Qi Chen You‐Sheng Yan Yi‐Peng Wang Dong‐Liang Zhang Cheng‐Hong Yin Qing Guo Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese population Molecular Genetics & Genomic Medicine acrofacial dysostosis DHODH gene Miller syndrome whole exome sequencing |
| title | Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese population |
| title_full | Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese population |
| title_fullStr | Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese population |
| title_full_unstemmed | Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese population |
| title_short | Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese population |
| title_sort | assessment of a novel variation in dhodh gene causing miller syndrome the first report in chinese population |
| topic | acrofacial dysostosis DHODH gene Miller syndrome whole exome sequencing |
| url | https://doi.org/10.1002/mgg3.2186 |
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