期刊
PEDIATRIC NEUROLOGY
卷 60, 期 -, 页码 83-87出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.pediatrneurol.2016.03.011
关键词
PEHO; encephalopathy; whole-exome sequencing; optic atrophy; neurodevelopmental disorder
资金
- US National Human Genome Research Institute (NHGRI)
- National Heart, Lung, and Blood Institute (NHBLI) [U54HG006542]
- NINDS [RO1 NS058529, K23NS078056]
- National Science Center, Poland [DEC-1012/06/M/NZ2/00101]
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 novo GNAO1 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.
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