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
AbstractBackground 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.
|Journal series||Pediatric Neurology, ISSN 0887-8994|
|Publication size in sheets||0.5|
|Keywords in English||PEHO;encephalopathy;whole-exome sequencing; optic atrophy;neurodevelopmental disorder|
|ASJC Classification||; ; ;|
|Project||Development 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
|Score|| = 25.0, 27-08-2020, ArticleFromJournal|
= 25.0, 27-08-2020, ArticleFromJournal
|Publication indicators||= 17; = 15; = 21.0; : 2016 = 0.971; : 2016 = 2.018 (2) - 2016=1.978 (5)|
|Citation count*||22 (2020-08-30)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.