A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report.
Case report
EFTUD2
Exonic splice enhancer variant
Mandibulofacial dysostosis with microcephaly
Synonymous splice variant
Whole-exome sequencing
de novo
Journal
BMC medical genetics
ISSN: 1471-2350
Titre abrégé: BMC Med Genet
Pays: England
ID NLM: 100968552
Informations de publication
Date de publication:
17 09 2020
17 09 2020
Historique:
received:
12
11
2019
accepted:
03
09
2020
entrez:
18
9
2020
pubmed:
19
9
2020
medline:
3
11
2020
Statut:
epublish
Résumé
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. 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. We present the first case of MFDM caused by a synonymous variant disrupting the donor splice site, leading to exon skipping.
Sections du résumé
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.
Identifiants
pubmed: 32943010
doi: 10.1186/s12881-020-01121-y
pii: 10.1186/s12881-020-01121-y
pmc: PMC7499997
doi:
Substances chimiques
EFTUD2 protein, human
0
Peptide Elongation Factors
0
Ribonucleoprotein, U5 Small Nuclear
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
182Subventions
Organisme : Université de Strasbourg
ID : IDEX UNISTRA
Pays : International
Organisme : Agence Nationale de la Recherche
ID : ANR-11-LABX-0070_TRANSPLANTEX
Pays : International
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