Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG
Abstract Background Dysregulation of the inositol cycle is implicated in a wide variety of human diseases, including developmental defects and neurological diseases. A homozygous frameshift mutation in IMPA1, coding for the enzyme inositol monophosphatase 1 (IMPase), has recently been associated wit...
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doaj-bd44d97df32443bda744ebbe51097de22020-11-25T01:52:37ZengBMCOrphanet Journal of Rare Diseases1750-11722019-01-0114111010.1186/s13023-018-0977-1Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEGChristopher P. Walker0Andre L. S. Pessoa1Thalita Figueiredo2Megan Rafferty3Uirá S. Melo4Paulo R. Nóbrega5Nicholas Murphy6Fernando Kok7Mayana Zatz8Silvana Santos9Raymond Y. Cho10Graduate School of Biomedical Sciences, University of Texas Health Science Center at HoustonHospital Infantil Albert SabinHuman Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Instituto de Biociências, Universidade de São Paulo (USP)Department of Psychiatry, Baylor College of MedicineHuman Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Instituto de Biociências, Universidade de São Paulo (USP)Federal University of CearáDepartment of Psychiatry, Baylor College of MedicineHuman Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Instituto de Biociências, Universidade de São Paulo (USP)Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Instituto de Biociências, Universidade de São Paulo (USP)Department of Biology, State University of Paraíba (UEPB)Department of Psychiatry, Baylor College of MedicineAbstract Background Dysregulation of the inositol cycle is implicated in a wide variety of human diseases, including developmental defects and neurological diseases. A homozygous frameshift mutation in IMPA1, coding for the enzyme inositol monophosphatase 1 (IMPase), has recently been associated with severe intellectual disability (ID) in a geographically isolated consanguineous family in Northeastern Brazil (Figueredo et al., 2016). However, the neurophysiologic mechanisms that mediate the IMPA1 mutation and associated ID phenotype have not been characterized. To this end, resting EEG (eyes-open and eyes-closed) was collected from the Figueredo et al. pedigree. Quantitative EEG measures, including mean power, dominant frequency and dominant frequency variability, were investigated for allelic associations using multivariate family-based association test using generalized estimating equations. Results We found that the IMPA1 mutation was associated with relative decreases in frontal theta band power as well as altered alpha-band variability with no regional specificity during the eyes-open condition. For the eyes-closed condition, there was altered dominant theta frequency variability in the central and parietal regions. Conclusions These findings represent the first human in vivo phenotypic assessment of brain function disturbances associated with a loss-of-function IMPA1 mutation, and thus an important first step towards an understanding the pathophysiologic mechanisms of intellectual disability associated with the mutation that affects this critical metabolic pathway.http://link.springer.com/article/10.1186/s13023-018-0977-1Inosotol monophosphataseIMPA1ElectroencephalographyEEGOscillations |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christopher P. Walker Andre L. S. Pessoa Thalita Figueiredo Megan Rafferty Uirá S. Melo Paulo R. Nóbrega Nicholas Murphy Fernando Kok Mayana Zatz Silvana Santos Raymond Y. Cho |
spellingShingle |
Christopher P. Walker Andre L. S. Pessoa Thalita Figueiredo Megan Rafferty Uirá S. Melo Paulo R. Nóbrega Nicholas Murphy Fernando Kok Mayana Zatz Silvana Santos Raymond Y. Cho Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG Orphanet Journal of Rare Diseases Inosotol monophosphatase IMPA1 Electroencephalography EEG Oscillations |
author_facet |
Christopher P. Walker Andre L. S. Pessoa Thalita Figueiredo Megan Rafferty Uirá S. Melo Paulo R. Nóbrega Nicholas Murphy Fernando Kok Mayana Zatz Silvana Santos Raymond Y. Cho |
author_sort |
Christopher P. Walker |
title |
Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG |
title_short |
Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG |
title_full |
Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG |
title_fullStr |
Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG |
title_full_unstemmed |
Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG |
title_sort |
loss-of-function mutation in inositol monophosphatase 1 (impa1) results in abnormal synchrony in resting-state eeg |
publisher |
BMC |
series |
Orphanet Journal of Rare Diseases |
issn |
1750-1172 |
publishDate |
2019-01-01 |
description |
Abstract Background Dysregulation of the inositol cycle is implicated in a wide variety of human diseases, including developmental defects and neurological diseases. A homozygous frameshift mutation in IMPA1, coding for the enzyme inositol monophosphatase 1 (IMPase), has recently been associated with severe intellectual disability (ID) in a geographically isolated consanguineous family in Northeastern Brazil (Figueredo et al., 2016). However, the neurophysiologic mechanisms that mediate the IMPA1 mutation and associated ID phenotype have not been characterized. To this end, resting EEG (eyes-open and eyes-closed) was collected from the Figueredo et al. pedigree. Quantitative EEG measures, including mean power, dominant frequency and dominant frequency variability, were investigated for allelic associations using multivariate family-based association test using generalized estimating equations. Results We found that the IMPA1 mutation was associated with relative decreases in frontal theta band power as well as altered alpha-band variability with no regional specificity during the eyes-open condition. For the eyes-closed condition, there was altered dominant theta frequency variability in the central and parietal regions. Conclusions These findings represent the first human in vivo phenotypic assessment of brain function disturbances associated with a loss-of-function IMPA1 mutation, and thus an important first step towards an understanding the pathophysiologic mechanisms of intellectual disability associated with the mutation that affects this critical metabolic pathway. |
topic |
Inosotol monophosphatase IMPA1 Electroencephalography EEG Oscillations |
url |
http://link.springer.com/article/10.1186/s13023-018-0977-1 |
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