Neonatal Alexander disease : novel GFAP mutation and comparison to previously published cases |
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Author: | Knuutinen, Oula1,2,3; Kousi, Maria4,5; Suo-Palosaari, Maria2,6; |
Organizations: |
1PEDEGO Research Unit, University of Oulu, Finland 2Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland 3Biocenter Oulu, University of Oulu, Finland
4Folkhälsan Institute of Genetics, Helsinki, Finland
5Center for Human Disease Modeling, Duke University Medical Center, Durham, North Carolina, United States 6Department of Diagnostic Radiology, Oulu University Hospital, Finland 7Department of Clinical Genetics, Oulu University Hospital, Finland 8Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu and Oulu University Hospital, Finland 9Clinic for Children and Adolescents, Oulu University Hospital, Finland 10Neuroscience Center, University of Helsinki, Finland 11Research Programs Unit, Molecular Neurology, University of Helsinki, Finland 12Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Finland |
Format: | article |
Version: | accepted version |
Access: | open |
Online Access: | PDF Full Text (PDF, 1.1 MB) |
Persistent link: | http://urn.fi/urn:nbn:fi-fe202001081465 |
Language: | English |
Published: |
Thieme,
2018
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Publish Date: | 2019-05-25 |
Description: |
AbstractAlexander disease (AxD) is a genetic leukodystrophy caused by GFAP mutations leading to astrocyte dysfunction. Neonatal AxD is a rare phenotype with onset in the first month of life. The proband, belonging to a large pedigree with dominantly inherited benign familial neonatal epilepsy (BFNE), had a phenotype distinct from the rest of the family, with hypotonia and macrocephaly in addition to drug-resistant neonatal seizures. The patient deteriorated and passed away at 6 weeks of age. The pathological and neuroimaging data were consistent with the diagnosis of AxD. Genetic analysis of the proband identified a novel de novo GFAP missense mutation and a KCNQ2 splice site mutation segregating with the BFNE phenotype in the family. The GFAP mutation was located in the coil 2B region of GFAP protein, similar to most neonatal-onset AxD cases with an early death. The clinical and neuroradiological features of the previously published neonatal AxD patients are presented. This study further supports the classification of neonatal-onset AxD as a distinct phenotype based on the age of onset. see all
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Series: |
Neuropediatrics |
ISSN: | 0174-304X |
ISSN-E: | 1439-1899 |
ISSN-L: | 0174-304X |
Volume: | 49 |
Issue: | 4 |
Pages: | 256 - 261 |
DOI: | 10.1055/s-0038-1649500 |
OADOI: | https://oadoi.org/10.1055/s-0038-1649500 |
Type of Publication: |
A1 Journal article – refereed |
Field of Science: |
3123 Gynaecology and paediatrics 3124 Neurology and psychiatry |
Subjects: | |
Funding: |
This work was supported by Folkhälsan Research Foundation. |
Copyright information: |
© 2018 Georg Thieme Verlag KG, Stuttgart · New York |