A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report
Abstract Background Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant genetic disease characterized by intellectual and growth retardations, as well as major microcephaly, induced by missense and splice site variants or microdeletions in the EFTUD2 gene. Case presentat...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-09-01
|
| Series: | BMC Medical Genetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12881-020-01121-y |
| _version_ | 1828898696828289024 |
|---|---|
| author | Arthur Jacob Jennifer Pasquier Raphael Carapito Frédéric Auradé Anne Molitor Philippe Froguel Khalid Fakhro Najeeb Halabi Géraldine Viot Seiamak Bahram Arash Rafii |
| author_facet | Arthur Jacob Jennifer Pasquier Raphael Carapito Frédéric Auradé Anne Molitor Philippe Froguel Khalid Fakhro Najeeb Halabi Géraldine Viot Seiamak Bahram Arash Rafii |
| author_sort | Arthur Jacob |
| collection | DOAJ |
| description | Abstract Background Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant genetic disease characterized by intellectual and growth retardations, as well as major microcephaly, induced by missense and splice site variants or microdeletions in the EFTUD2 gene. Case presentation Here, we investigate the case of a young girl with symptoms of MFDM and a normal karyotype. Whole-exome sequencing of the family was performed to identify genetic alterations responsible for this phenotype. We identified a de novo synonymous variant in the EFTUD2 gene. We demonstrated that this synonymous variant disrupts the donor splice-site in intron 9 resulting in the skipping of exon 9 and a frameshift that leads to a premature stop codon. Conclusions We present the first case of MFDM caused by a synonymous variant disrupting the donor splice site, leading to exon skipping. |
| first_indexed | 2024-12-13T15:19:41Z |
| format | Article |
| id | doaj.art-d9d64217f70444de95fa1d71d02b591e |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-13T15:19:41Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-d9d64217f70444de95fa1d71d02b591e2022-12-21T23:40:36ZengBMCBMC Medical Genetics1471-23502020-09-012111810.1186/s12881-020-01121-yA de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case reportArthur Jacob0Jennifer Pasquier1Raphael Carapito2Frédéric Auradé3Anne Molitor4Philippe Froguel5Khalid Fakhro6Najeeb Halabi7Géraldine Viot8Seiamak Bahram9Arash Rafii10Univ. Lille, CNRS, CHU Lille, Institut Pasteur de Lille, UMR 8199 – EGIDStem Cell and Microenvironment Laboratory, Weill Cornell Medicine-Qatar, Education City, Qatar FoundationLaboratoire d’ImmunoRhumatologie Moléculaire, plateforme GENOMAX, INSERM UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), LabEx TRANSPLANTEX, Université de StrasbourgINSERM IMRB U955-E10, UPEC - Université Paris Est, Faculté de MédicineLaboratoire d’ImmunoRhumatologie Moléculaire, plateforme GENOMAX, INSERM UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), LabEx TRANSPLANTEX, Université de StrasbourgUniv. Lille, CNRS, CHU Lille, Institut Pasteur de Lille, UMR 8199 – EGIDEpigenetics Cardiovascular Laboratory, Department of Genetic Medicine, Weill Cornell Medicine-QatarStem cell and microenvironment laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar FoundationGynécologie Obstétrique, HUPC, Hôpital Cochin, HUPC, Assistance Publique - Hôpitaux de ParisLaboratoire d’ImmunoRhumatologie Moléculaire, plateforme GENOMAX, INSERM UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), LabEx TRANSPLANTEX, Université de StrasbourgStem cell and microenvironment laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar FoundationAbstract Background Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant genetic disease characterized by intellectual and growth retardations, as well as major microcephaly, induced by missense and splice site variants or microdeletions in the EFTUD2 gene. Case presentation Here, we investigate the case of a young girl with symptoms of MFDM and a normal karyotype. Whole-exome sequencing of the family was performed to identify genetic alterations responsible for this phenotype. We identified a de novo synonymous variant in the EFTUD2 gene. We demonstrated that this synonymous variant disrupts the donor splice-site in intron 9 resulting in the skipping of exon 9 and a frameshift that leads to a premature stop codon. Conclusions We present the first case of MFDM caused by a synonymous variant disrupting the donor splice site, leading to exon skipping.http://link.springer.com/article/10.1186/s12881-020-01121-yEFTUD2Mandibulofacial dysostosis with microcephalyde novoSynonymous splice variantExonic splice enhancer variantWhole-exome sequencing |
| spellingShingle | Arthur Jacob Jennifer Pasquier Raphael Carapito Frédéric Auradé Anne Molitor Philippe Froguel Khalid Fakhro Najeeb Halabi Géraldine Viot Seiamak Bahram Arash Rafii A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report BMC Medical Genetics EFTUD2 Mandibulofacial dysostosis with microcephaly de novo Synonymous splice variant Exonic splice enhancer variant Whole-exome sequencing |
| title | A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report |
| title_full | A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report |
| title_fullStr | A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report |
| title_full_unstemmed | A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report |
| title_short | A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report |
| title_sort | de novo synonymous variant in eftud2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly case report |
| topic | EFTUD2 Mandibulofacial dysostosis with microcephaly de novo Synonymous splice variant Exonic splice enhancer variant Whole-exome sequencing |
| url | http://link.springer.com/article/10.1186/s12881-020-01121-y |
| work_keys_str_mv | AT arthurjacob adenovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT jenniferpasquier adenovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT raphaelcarapito adenovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT fredericaurade adenovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT annemolitor adenovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT philippefroguel adenovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT khalidfakhro adenovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT najeebhalabi adenovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT geraldineviot adenovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT seiamakbahram adenovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT arashrafii adenovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT arthurjacob denovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT jenniferpasquier denovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT raphaelcarapito denovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT fredericaurade denovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT annemolitor denovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT philippefroguel denovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT khalidfakhro denovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT najeebhalabi denovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT geraldineviot denovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT seiamakbahram denovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport AT arashrafii denovosynonymousvariantineftud2disruptsnormalsplicingandcausesmandibulofacialdysostosiswithmicrocephalycasereport |