title: De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive.
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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Miraca Genetics Laboratories, Houston, TX 77021, USA.
authors.forename: Mari J
authors.initials: MJ
authors.lastname: Tokita
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Miraca Genetics Laboratories, Houston, TX 77021, USA.
authors.forename: Alicia A
authors.initials: AA
authors.lastname: Braxton
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Yunru
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Lewis
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, 44093 Nantes Cedex 1, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Vincent
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, 44093 Nantes Cedex 1, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Küry
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, 44093 Nantes Cedex 1, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Besnard
authors.affiliation: 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.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, 44093 Nantes Cedex 1, France.
authors.forename: Xénia
authors.initials: X
authors.lastname: Latypova
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, 44093 Nantes Cedex 1, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bézieau
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Miraca Genetics Laboratories, Houston, TX 77021, USA.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Genetic Center, Akron Children's Hospital, Akron, OH 44302, USA.
authors.forename: Connie S
authors.initials: CS
authors.lastname: Motter
authors.affiliation: Genetic Center, Akron Children's Hospital, Akron, OH 44302, USA.
authors.forename: Catherine Ward
authors.initials: CW
authors.lastname: Melver
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Nathaniel H
authors.initials: NH
authors.lastname: Robin
authors.affiliation: University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Infante
authors.affiliation: Baylor Miraca Genetics Laboratories, Houston, TX 77021, USA; University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Marianne
authors.initials: M
authors.lastname: McGuire
authors.affiliation: University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Areeg
authors.initials: A
authors.lastname: El-Gharbawy
authors.affiliation: Children's Hospital of San Antonio, San Antonio, TX 78207, USA.
authors.forename: Rebecca O
authors.initials: RO
authors.lastname: Littlejohn
authors.affiliation: Children's Hospital of San Antonio, San Antonio, TX 78207, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: McLean
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Miraca Genetics Laboratories, Houston, TX 77021, USA.
authors.forename: Weimin
authors.initials: W
authors.lastname: Bi
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Seema R
authors.initials: SR
authors.lastname: Lalani
authors.affiliation: 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.
authors.forename: Daryl A
authors.initials: DA
authors.lastname: Scott
authors.affiliation: 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.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Eng
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Miraca Genetics Laboratories, Houston, TX 77021, USA.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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: schaaf@bcm.edu.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Schaaf
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Miraca Genetics Laboratories, Houston, TX 77021, USA. Electronic address: mwalkiew@bcm.edu.
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Walkiewicz
mesh_terms: D000293:Adolescent; D001921:Brain / Q000002:abnormalities; D002648:Child; D002675:Child, Preschool; D000013:Congenital Abnormalities / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005183:Failure to Thrive / Q000235:genetics*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D015778:Minor Histocompatibility Antigens; C088203:SON protein, human