De novo mutations in PURA are associated with hypotonia and developmental delay
- Akemi J. Tanaka1,
- Renkui Bai2,
- Megan T. Cho2,
- Kwame Anyane-Yeboa1,
- Priyanka Ahimaz1,
- Ashley L. Wilson1,
- Fran Kendall3,4,
- Beverly Hay5,
- Timothy Moss6,
- Monica Nardini6,
- Mislen Bauer7,
- Kyle Retterer2,
- Jane Juusola2 and
- Wendy K. Chung1,8
- 1Department of Pediatrics, Columbia University Medical Center, New York, New York 10029, USA;
- 2GeneDx, Gaithersburg, Maryland 20877, USA;
- 3VMP Genetics, Roswell, Georgia 30076, USA;
- 4Department of Kinesiology, University of Georgia, Athens, Georgia 30605, USA;
- 5Division of Genetics, UMass Memorial Medical Center, Worcester, Massachusetts 01655, USA;
- 6Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, Ohio 44195, USA;
- 7Department of Genetics, Miami Children's Hospital, Miami, Florida 33155, USA;
- 8Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA
- Corresponding author: wkc15{at}columbia.edu
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.
- central hypotonia
- generalized clonic seizures
- generalized tonic seizures
- severe global developmental delay
- Received March 24, 2015.
- Accepted May 18, 2015.
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