title: De novo mutations in PURA are associated with hypotonia and developmental delay.
abstract: PURA is the leading candidate gene responsible for the developmental phenotype in the 5q31.3 microdeletion syndrome. De novo mutations in PURA were recently reported in 15 individuals with developmental features similar to the 5q31.3 microdeletion syndrome. Here we describe six unrelated children who were identified by clinical whole-exome sequencing (WES) to have novel de novo variants in PURA with a similar phenotype of hypotonia and developmental delay and frequently associated with seizures. The protein Purα (encoded by PURA) is involved in neuronal proliferation, dendrite maturation, and the transport of mRNA to translation sites during neuronal development. Mutations in PURA may alter normal brain development and impair neuronal function, leading to developmental delay and the seizures observed in patients with mutations in PURA.
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York 10029, USA;
authors.forename: Akemi J
authors.initials: AJ
authors.lastname: Tanaka
authors.affiliation: GeneDx, Gaithersburg, Maryland 20877, USA;
authors.forename: Renkui
authors.initials: R
authors.lastname: Bai
authors.affiliation: GeneDx, Gaithersburg, Maryland 20877, USA;
authors.forename: Megan T
authors.initials: MT
authors.lastname: Cho
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York 10029, USA;
authors.forename: Kwame
authors.initials: K
authors.lastname: Anyane-Yeboa
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York 10029, USA;
authors.forename: Priyanka
authors.initials: P
authors.lastname: Ahimaz
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York 10029, USA;
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Wilson
authors.affiliation: VMP Genetics, Roswell, Georgia 30076, USA;; Department of Kinesiology, University of Georgia, Athens, Georgia 30605, USA;
authors.forename: Fran
authors.initials: F
authors.lastname: Kendall
authors.affiliation: Division of Genetics, UMass Memorial Medical Center, Worcester, Massachusetts 01655, USA;
authors.forename: Beverly
authors.initials: B
authors.lastname: Hay
authors.affiliation: Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, Ohio 44195, USA;
authors.forename: Timothy
authors.initials: T
authors.lastname: Moss
authors.affiliation: Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, Ohio 44195, USA;
authors.forename: Monica
authors.initials: M
authors.lastname: Nardini
authors.affiliation: Department of Genetics, Miami Children's Hospital, Miami, Florida 33155, USA;
authors.forename: Mislen
authors.initials: M
authors.lastname: Bauer
authors.affiliation: GeneDx, Gaithersburg, Maryland 20877, USA;
authors.forename: Kyle
authors.initials: K
authors.lastname: Retterer
authors.affiliation: GeneDx, Gaithersburg, Maryland 20877, USA;
authors.forename: Jane
authors.initials: J
authors.lastname: Juusola
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York 10029, 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: central hypotonia; generalized clonic seizures; generalized tonic seizures; severe global developmental delay