Expanding the neurodevelopmental phenotype of PURA syndrome

Autor: Brynn Lape, Karen W. Gripp, Alex R. Paciorkowski, Wen-Hann Tan, Margot R.F. Reijnders, Diana Baralle, Bo Hoon Lee, Christopher J. Stodgell, Richard J. Leventer, Chin-To Fong, Wendy E. Smith, David Hunt, Eric D. Marsh, Emily Tuttle, Loisa Bennetto, Ahm M. Huq, Kelly Q. Minks, Stephanie A. Coury, Rupal I. Mehta, Orestes Solis, Oluwatobi Abubakare, Jennifer M. Kwon
Rok vydání: 2017
Předmět:
Adult
Male
0301 basic medicine
Pediatrics
medicine.medical_specialty
Adolescent
DNA Mutational Analysis
Encephalopathy
Article
Young Adult
03 medical and health sciences
Epilepsy
All institutes and research themes of the Radboud University Medical Center
0302 clinical medicine
Intellectual Disability
Exome Sequencing
Intellectual disability
Genetics
Humans
Medicine
Global developmental delay
Child
Genetic Association Studies
Genetics (clinical)
Exome sequencing
Brain Diseases
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
business.industry
Disease Management
Facies
Infant
Syndrome
medicine.disease
Magnetic Resonance Imaging
White Matter
DNA-Binding Proteins
Phenotype
030104 developmental biology
Neonatal hypotonia
Child
Preschool
Cohort
Chromosomes
Human
Pair 5
Autism
Female
Chromosome Deletion
business
030217 neurology & neurosurgery
Transcription Factors
Zdroj: American Journal of Medical Genetics. Part A, 176, 56-67
American Journal of Medical Genetics. Part A, 176, 1, pp. 56-67
ISSN: 1552-4825
DOI: 10.1002/ajmg.a.38521
Popis: PURA syndrome is a recently described developmental encephalopathy presenting with neonatal hypotonia, feeding difficulties, global developmental delay, severe intellectual disability, and frequent apnea and epilepsy. We describe 18 new individuals with heterozygous sequence variations in PURA. A neuromotor disorder starting with neonatal hyptonia, but ultimately allowing delayed progression to walking, was present in nearly all individuals. Congenital apnea was present in 56% during infancy, but all cases in this cohort resolved during the first year of life. Feeding difficulties were frequently reported, with gastrostomy tube placement required in 28%. Epilepsy was present in 50% of the subjects, including infantile spasms and Lennox-Gastaut syndrome. Skeletal complications were found in 39%. Disorders of gastrointestinal motility and nystagmus were also recurrent features. Autism was diagnosed in one individual, potentially expanding the neurodevelopmental phenotype associated with this syndrome. However, we did not find additional PURA sequence variations in a cohort of 120 subjects with autism. We also present the first neuropathologic studies of PURA syndrome, and describe chronic inflammatory changes around the arterioles within the deep white matter. We did not find significant correlations between mutational class and severity, nor between location of the sequence variation in PUR repeat domains. Further studies are required in larger cohorts of subjects with PURA syndrome to clarify these genotype-phenotype associations.
Databáze: OpenAIRE
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