title: MED13L haploinsufficiency syndrome: A de novo frameshift and recurrent intragenic deletions due to parental mosaicism.
abstract: MED13L haploinsufficiency syndrome is a clinical condition manifesting intellectual disability and developmental delay in association with various complications including congenital heart defects and dysmorphic features. Most of the previously reported patients showed de novo loss-of-function mutations in MED13L. Additional three patients with MED13L haploinsufficiency syndrome were identified here in association with rare complications. One patient had a de novo deletion (c.257delT) and T2-weighted high intensity in the occipital white matter on magnetic resonance imaging. Two siblings exhibited an intragenic deletion involving exons 3-14, which led to an in-frame deletion in MED13L. The deletion was inherited from their carrier mother who possessed low frequency mosaicism. The older sister of the siblings showed craniosynostosis; this condition has never been reported in patients with MED13L haploinsufficiency syndrome. Dysmorphic features were observed in these patients; however, most of the findings were nonspecific. Further information would be necessary to understand this clinical condition better.
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.|Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Toshiyuki
authors.identifier: http://orcid.org/0000-0002-9484-3505
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.|Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ondo
authors.affiliation: Department of Pediatrics, Osaka Medical College, Osaka, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Shimakawa
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Nobuhiko
authors.identifier: http://orcid.org/0000-0001-5415-656X
authors.initials: N
authors.lastname: Okamoto
mesh_terms: D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D016368:Frameshift Mutation; D057895:Haploinsufficiency / Q000235:genetics; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D056892:Mediator Complex / Q000235:genetics*; D009030:Mosaicism; D017384:Sequence Deletion; D035781:Siblings
chemical_list: C480067:MED13L protein, human; D056892:Mediator Complex
keywords: MED13L haploinsufficiency syndrome; craniosynostosis; intellectual disability; loss-of-function; mosaic