A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report

BMC Medical Genetics

Khalid Fakhro¹  Géraldine Viot²  Frédéric Auradé³  Anne Molitor⁴  Raphael Carapito⁴  Seiamak Bahram⁴  Jennifer Pasquier⁵  Najeeb Halabi⁶  Arash Rafii⁷  Arthur Jacob⁸  Philippe Froguel⁹ 

[1]Epigenetics Cardiovascular Laboratory, Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar

[2]Department of Human Genetics, Sidra Medical and Research Center, Doha, Qatar

[3]Gynécologie Obstétrique, HUPC, Hôpital Cochin, HUPC, Assistance Publique - Hôpitaux de Paris, Paris, France

[4]INSERM IMRB U955-E10, UPEC - Université Paris Est, Faculté de Médicine, 94000, Créteil, France

[5]Laboratoire 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 Strasbourg, 4 rue Kirschleger, 67085, Strasbourg, France

[6]Stem Cell and Microenvironment Laboratory, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar

[7]Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UMR_S 938, Centre de Recherche Saint-Antoine, Team Cancer Biology and Therapeutics, Institut Universitaire de Cancérologie, Sorbonne Université, F-75012, Paris, France

[8]Nice Breast institute, 57 bld de la Californie, 06000, Nice, France

[9]Stem cell and microenvironment laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar

[10]Stem cell and microenvironment laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar

[11]Department Genetic Medicine, Weill Cornell Medical College, New York, NY, USA

[12]Univ. Lille, CNRS, CHU Lille, Institut Pasteur de Lille, UMR 8199 – EGID, F-59000, Lille, France

[13]Univ. Lille, CNRS, CHU Lille, Institut Pasteur de Lille, UMR 8199 – EGID, F-59000, Lille, France

[14]Department of Genomics of Common Disease, School of Public Health, Imperial College, South Kensington Campus, SW7 2AZ, London, UK

关键词: EFTUD2;    Mandibulofacial dysostosis with microcephaly;    de novo;    Synonymous splice variant;    Exonic splice enhancer variant;    Whole-exome sequencing;    Case report;   

DOI  :  10.1186/s12881-020-01121-y

来源: Springer

【 摘 要 】

BackgroundMandibulofacial 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 presentationHere, 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.ConclusionsWe present the first case of MFDM caused by a synonymous variant disrupting the donor splice site, leading to exon skipping.

【 授权许可】

CC BY