2. Academic Validation
  3. De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive

De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive

  • Am J Hum Genet. 2016 Sep 1;99(3):720-727. doi: 10.1016/j.ajhg.2016.06.035.
Mari J Tokita 1,  Alicia A Braxton 1,  Yunru Shao 2,  Andrea M Lewis 2,  Marie Vincent 3,  Sébastien Küry 3,  Thomas Besnard 3,  Bertrand Isidor 4,  Xénia Latypova 3,  Stéphane Bézieau 3,  Pengfei Liu 1,  Connie S Motter 5,  Catherine Ward Melver 5,  Nathaniel H Robin 6,  Elena M Infante 7,  Marianne McGuire 8,  Areeg El-Gharbawy 7,  Rebecca O Littlejohn 9,  Scott D McLean 9,  Weimin Bi 1,  Carlos A Bacino 2,  Seema R Lalani 2,  Daryl A Scott 10,  Christine M Eng 11,  Yaping Yang 1,  Christian P Schaaf 12,  Magdalena A Walkiewicz 13
Affiliations

Affiliations

  • 1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Miraca Genetics Laboratories, Houston, TX 77021, USA.
  • 2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
  • 3 Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, 44093 Nantes Cedex 1, France.
  • 4 Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, 44093 Nantes Cedex 1, France; INSERM UMR-S 957, 1 Rue Gaston Veil, 44035 Nantes, France.
  • 5 Genetic Center, Akron Children's Hospital, Akron, OH 44302, USA.
  • 6 Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • 7 University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.
  • 8 Baylor Miraca Genetics Laboratories, Houston, TX 77021, USA; University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.
  • 9 Children's Hospital of San Antonio, San Antonio, TX 78207, USA.
  • 10 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
  • 11 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Miraca Genetics Laboratories, Houston, TX 77021, USA; Texas Children's Hospital, Houston, TX 77030, USA.
  • 12 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA. Electronic address: [email protected].
  • 13 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Miraca Genetics Laboratories, Houston, TX 77021, USA. Electronic address: [email protected].
PMID: 27545676 DOI: 10.1016/j.ajhg.2016.06.035
Abstract

SON is a key component of the spliceosomal complex and a critical mediator of constitutive and alternative splicing. Additionally, SON has been shown to influence cell-cycle progression, genomic integrity, and maintenance of pluripotency in stem cell populations. The clear functional relevance of SON in coordinating essential cellular processes and its presence in diverse human tissues suggests that intact SON might be crucial for normal growth and development. However, the phenotypic effects of deleterious germline variants in SON have not been clearly defined. Herein, we describe seven unrelated individuals with de novo variants in SON and propose that deleterious variants in SON are associated with a severe multisystem disorder characterized by developmental delay, persistent feeding difficulties, and congenital malformations, including brain anomalies.

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