Mutations in PURA cause profound neonatal hypotonia, seizures, and encephalopathy in 5q31.3 microdeletion syndrome

Seema R Lalani; Jing Zhang; Christian P Schaaf; Chester W Brown; Pilar Magoulas; Anne Chun-Hui Tsai; Areeg El-Gharbawy; Klaas J Wierenga; Dennis Bartholomew; Chin-To Fong; Tina Barbaro-Dieber; Mary K Kukolich; Lindsay C Burrage; Elise Austin; Kory Keller; Matthew Pastore; Fabio Fernandez; Timothy Lotze; Angus Wilfong; Gabriela Purcarin; Wenmiao Zhu; William J Craigen; Marianne McGuire; Mahim Jain; Erin Cooney; Mahshid Azamian; Matthew N Bainbridge; Donna M Muzny; Eric Boerwinkle; Richard E Person; Zhiyv Niu; Christine M Eng; James R Lupski; Richard A Gibbs; Arthur L Beaudet; Yaping Yang; Meng C Wang; Fan Xia

doi:10.1016/j.ajhg.2014.09.014

Mutations in PURA cause profound neonatal hypotonia, seizures, and encephalopathy in 5q31.3 microdeletion syndrome

Am J Hum Genet. 2014 Nov 6;95(5):579-83. doi: 10.1016/j.ajhg.2014.09.014. Epub 2014 Oct 16.

Authors

Seema R Lalani¹, Jing Zhang², Christian P Schaaf³, Chester W Brown⁴, Pilar Magoulas², Anne Chun-Hui Tsai⁵, Areeg El-Gharbawy⁶, Klaas J Wierenga⁷, Dennis Bartholomew⁸, Chin-To Fong⁹, Tina Barbaro-Dieber¹⁰, Mary K Kukolich¹⁰, Lindsay C Burrage², Elise Austin², Kory Keller⁵, Matthew Pastore⁸, Fabio Fernandez¹¹, Timothy Lotze¹¹, Angus Wilfong¹¹, Gabriela Purcarin¹², Wenmiao Zhu², William J Craigen², Marianne McGuire², Mahim Jain², Erin Cooney², Mahshid Azamian², Matthew N Bainbridge¹³, Donna M Muzny¹⁴, Eric Boerwinkle¹⁵, Richard E Person¹⁶, Zhiyv Niu¹⁶, Christine M Eng¹⁶, James R Lupski¹⁷, Richard A Gibbs¹⁸, Arthur L Beaudet², Yaping Yang¹⁶, Meng C Wang¹⁹, Fan Xia²⁰

Affiliations

¹ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: seemal@bcm.edu.
² Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
³ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
⁴ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
⁵ Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, OR 97239, USA.
⁶ Department of Pediatrics and Division of Medical Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
⁷ Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
⁸ Division of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, OH 43205, USA.
⁹ Clinic of Inherited Metabolic Disease, University of Rochester Medical Center, Rochester, NY 14642, USA.
¹⁰ Clinical Genetics, Cook Children's Hospital, Fort Worth, TX 76102, USA.
¹¹ Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
¹² Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
¹³ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
¹⁴ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Whole Genome Laboratory, Baylor College of Medicine, Houston, TX 77030, USA.
¹⁵ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Human Genetics Center, University of Texas Health Science Center, Houston, TX 77030, USA.
¹⁶ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Whole Genome Laboratory, Baylor College of Medicine, Houston, TX 77030, USA.
¹⁷ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Texas Children's Hospital, Houston, TX 77030, USA.
¹⁸ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
¹⁹ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.
²⁰ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Whole Genome Laboratory, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: fxia@bcm.edu.

Abstract

5q31.3 microdeletion syndrome is characterized by neonatal hypotonia, encephalopathy with or without epilepsy, and severe developmental delay, and the minimal critical deletion interval harbors three genes. We describe 11 individuals with clinical features of 5q31.3 microdeletion syndrome and de novo mutations in PURA, encoding transcriptional activator protein Pur-α, within the critical region. These data implicate causative PURA mutations responsible for the severe neurological phenotypes observed in this syndrome.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Abnormalities, Multiple / genetics*
Amino Acid Sequence
Animals
Base Sequence
Caenorhabditis elegans / genetics
Chromosome Deletion*
Chromosome Mapping
Chromosomes, Human, Pair 5 / genetics*
DNA-Binding Proteins / genetics*
Humans
Molecular Sequence Data
Muscle Hypotonia / genetics*
Mutation / genetics
Seizures / genetics*
Sequence Analysis, DNA
Syndrome
Transcription Factors / genetics*

Substances

DNA-Binding Proteins
PURA protein, human
Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding