Prenatal diagnostic approaches diagnosed craniosynostosis and identified a novel nonsense variant in SMAD6 in a Chinese fetus
Copyright © 2023. Published by Elsevier B.V..
Craniosynostosis is one of the most common congenital craniofacial birth defects. The genetic etiology is complex, involving syndromic developmental diseases, chromosomal abnormalities, and monogenic non-syndromic diseases. Herein, we presented a proband of craniosynostosis, who firstly displayed structural abnormalities. This research conducted dynamic ultrasound monitoring a fetus with gradually developing intrauterine growth retardation (IUGR). A novel de novo variant c.41G > A: p.W14* in SMAD6 was identified by pedigree analysis and genetic examination approaches. Recombinant plasmid carrying wild-type sequence and mutant that carries c.41G > A in SMAD6 were constructed and transfected into HEK293T cells. mRNA and protein expression of SMAD6 were reduced in SMAD6 mutants compared to the wild type. Cycloheximide (CHX) treatment and si-UPF1 transfection rescued the SMAD6 mRNA expression in the mutant construct, indicating that c.41G > A: p.W14* in SMAD6 triggered nonsense-mediated mRNA degradation (NMD) process and thus led to haploinsufficiency of the protein product. Our study demonstrated that whole-exome sequencing (WES) was a powerful tool for further diagnosis and etiological identification once fetal malformation was detected by ultrasound. Novel de novo c.41G > A: p.W14* in SMAD6 is pathogenic and potentially leads to craniosynostosis via NMD process.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:896 |
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| Enthalten in: |
Gene - 896(2024) vom: 20. Jan., Seite 147994 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hong, Zhidan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.01.2024 Date Revised 12.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.gene.2023.147994 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Prenatal diagnostic approaches diagnosed craniosynostosis and identified a novel nonsense variant in SMAD6 in a Chinese fetus |
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| 520 | |a Copyright © 2023. Published by Elsevier B.V. | ||
| 520 | |a Craniosynostosis is one of the most common congenital craniofacial birth defects. The genetic etiology is complex, involving syndromic developmental diseases, chromosomal abnormalities, and monogenic non-syndromic diseases. Herein, we presented a proband of craniosynostosis, who firstly displayed structural abnormalities. This research conducted dynamic ultrasound monitoring a fetus with gradually developing intrauterine growth retardation (IUGR). A novel de novo variant c.41G > A: p.W14* in SMAD6 was identified by pedigree analysis and genetic examination approaches. Recombinant plasmid carrying wild-type sequence and mutant that carries c.41G > A in SMAD6 were constructed and transfected into HEK293T cells. mRNA and protein expression of SMAD6 were reduced in SMAD6 mutants compared to the wild type. Cycloheximide (CHX) treatment and si-UPF1 transfection rescued the SMAD6 mRNA expression in the mutant construct, indicating that c.41G > A: p.W14* in SMAD6 triggered nonsense-mediated mRNA degradation (NMD) process and thus led to haploinsufficiency of the protein product. Our study demonstrated that whole-exome sequencing (WES) was a powerful tool for further diagnosis and etiological identification once fetal malformation was detected by ultrasound. Novel de novo c.41G > A: p.W14* in SMAD6 is pathogenic and potentially leads to craniosynostosis via NMD process | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Craniosynostosis | |
| 650 | 4 | |a Genetics | |
| 650 | 4 | |a Novel variant | |
| 650 | 4 | |a Prenatal diagnosis | |
| 650 | 4 | |a SMAD6 | |
| 650 | 4 | |a Whole-exome sequencing | |
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| 700 | 1 | |a Duan, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Huanyu |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yuanzhen |e verfasserin |4 aut | |
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