title: De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features.
abstract: We identified five unrelated individuals with significant global developmental delay and intellectual disability (ID), dysmorphic facial features and frequent microcephaly, and de novo predicted loss-of-function variants in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). Our findings are consistent with recently reported de novo mutations in CHAMP1 in five other individuals with similar features. CHAMP1 is a zinc finger protein involved in kinetochore-microtubule attachment and is required for regulating the proper alignment of chromosomes during metaphase in mitosis. Mutations in CHAMP1 may affect cell division and hence brain development and function, resulting in developmental delay and ID.
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA;
authors.forename: Akemi J
authors.initials: AJ
authors.lastname: Tanaka
authors.affiliation: GeneDx, Gaithersburg, Maryland 20877, USA;
authors.forename: Megan T
authors.initials: MT
authors.lastname: Cho
authors.affiliation: GeneDx, Gaithersburg, Maryland 20877, USA;
authors.forename: Kyle
authors.initials: K
authors.lastname: Retterer
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina 29646, USA;
authors.forename: Julie R
authors.initials: JR
authors.lastname: Jones
authors.affiliation: Boston Children's Hospital, Boston, Massachusetts 02115, USA;
authors.forename: Catherine
authors.initials: C
authors.lastname: Nowak
authors.affiliation: Boston Children's Hospital, Boston, Massachusetts 02115, USA;
authors.forename: Jessica
authors.initials: J
authors.lastname: Douglas
authors.affiliation: Duke University Medical Center, Durham, North Carolina 27710, USA;
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Jiang
authors.affiliation: Duke University Medical Center, Durham, North Carolina 27710, USA;
authors.forename: Allyn
authors.initials: A
authors.lastname: McConkie-Rosell
authors.affiliation: Arkansas Children's Hospital, Little Rock, Arkansas 72202, USA;
authors.forename: G Bradley
authors.initials: GB
authors.lastname: Schaefer
authors.affiliation: Arkansas Children's Hospital, Little Rock, Arkansas 72202, USA;
authors.forename: Julie
authors.initials: J
authors.lastname: Kaylor
authors.affiliation: Divisions of Medical Genetics and Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA;
authors.forename: Omar A
authors.initials: OA
authors.lastname: Rahman
authors.affiliation: GeneDx, Gaithersburg, Maryland 20877, USA;
authors.forename: Aida
authors.initials: A
authors.lastname: Telegrafi
authors.affiliation: GeneDx, Gaithersburg, Maryland 20877, USA;
authors.forename: Bethany
authors.initials: B
authors.lastname: Friedman
authors.affiliation: GeneDx, Gaithersburg, Maryland 20877, USA;
authors.forename: Ganka
authors.initials: G
authors.lastname: Douglas
authors.affiliation: GeneDx, Gaithersburg, Maryland 20877, USA;
authors.forename: Kristin G
authors.initials: KG
authors.lastname: Monaghan
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA;; Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
keywords: congenital microcephaly; intellectual disability, severe; severe global developmental delay