PEHO Syndrome May Represent Phenotypic Expansion at the Severe End of the Early-Onset Encephalopathies

Pawel Gawlinski , Renata Posmyk , Tomasz Gambin , Danuta Sielicka , Monika Chorazy , Beata Nowakowska , Shalini N. Jhangiani , Donna M. Muzny , Monika Bekiesinska-Figatowska , Jerzy Bal , Eric Boerwinkle , Richard A. Gibbs , Wojciech Wiszniewski , James R. Lupski

Abstract

Background Progressive encephalopathy with edema, hypsarrhythmia and optic atrophy (PEHO) syndrome is a distinct neurodevelopmental disorder. Patients without optic nerve atrophy and brain imaging abnormalities but fulfilling other PEHO criteria are often described as a PEHO-like syndrome. The molecular bases of both clinically defined conditions remain unknown in spite of the widespread application of genome analyses in both clinic and research. Methods We enrolled two patients with a prior diagnosis of PEHO and two individuals with PEHO-like syndrome. All four individuals subsequently underwent whole-exome sequencing and comprehensive genomic analysis. Results We identified disease-causing mutations in known genes associated with neurodevelopmental disorders including GNAO1 and CDKL5 in two of four individuals. One patient with PEHO syndrome and a de novoGNAO1 mutation was found to have an additional de novo mutation in HESX1 that is associated with optic atrophy. Conclusions We hypothesize that PEHO and PEHO-like syndrome may represent a severe end of the spectrum of the early-onset encephalopathies and, in some instances, its complex phenotype may result from an aggregated effect of mutations at two loci.
Author Pawel Gawlinski - Department of Diagnostic Imaging, Institute of Mother and Child, Warsaw, Poland
Pawel Gawlinski,,
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, Renata Posmyk - Department of Clinical Genetics, Podlaskie Medical Center, Bialystok, Poland
Renata Posmyk,,
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, Tomasz Gambin II
Tomasz Gambin,,
- The Institute of Computer Science
, Danuta Sielicka - Department of Pediatric Ophthalmology, Children's University Hospital, Bialystok, Poland
Danuta Sielicka,,
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, Monika Chorazy - Department of Neurology, Medical University Hospital, Bialystok, Poland
Monika Chorazy,,
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, Beata Nowakowska - Department of Diagnostic Imaging, Institute of Mother and Child, Warsaw, Poland
Beata Nowakowska,,
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, Shalini N. Jhangiani - Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
Shalini N. Jhangiani,,
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, Donna M. Muzny - Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
Donna M. Muzny,,
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, Monika Bekiesinska-Figatowska - Department of Diagnostic Imaging, Institute of Mother and Child, Warsaw, Poland
Monika Bekiesinska-Figatowska,,
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, Jerzy Bal - Institute of Mother and Child, Department of Diagnostic Imaging (IMD/ZDO)
Jerzy Bal ,,
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et al.`
Journal seriesPediatric Neurology, ISSN 0887-8994
Issue year2016
Vol60
Pages83-87
Publication size in sheets0.5
Keywords in EnglishPEHO;encephalopathy;whole-exome sequencing; optic atrophy;neurodevelopmental disorder
DOIDOI:10.1016/j.pediatrneurol.2016.03.011
URL http://dx.doi.org/10.1016/j.pediatrneurol.2016.03.011
projectDevelopment of new algorithms in the areas of software and computer architecture, artificial intelligence and information systems and computer graphics . Project leader: Rybiński Henryk, , Phone: +48 22 234 7731, start date 18-05-2015, end date 30-11-2016, II/2015/DS/1, Completed
WEiTI Działalność statutowa
Languageen angielski
File
PEHO.pdf 743.22 KB
Score (nominal)25
ScoreMinisterial score = 25.0, 27-03-2017, ArticleFromJournal
Ministerial score (2013-2016) = 25.0, 27-03-2017, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 2.018 (2) - 2016=1.978 (5)
Citation count*9 (2018-06-20)
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