Novel Homozygous Mutation of the AIMP1 Gene: A Milder Neuroimaging Phenotype With Preservation of the Deep White Matter.
Adolescent
Adult
Aspartic Acid
/ analogs & derivatives
Child
Consanguinity
Cytokines
/ genetics
Developmental Disabilities
/ etiology
Epilepsy
/ etiology
Failure to Thrive
/ etiology
Female
Humans
Magnetic Resonance Imaging
Male
Microcephaly
/ etiology
Mutation
Neoplasm Proteins
/ genetics
Neurodegenerative Diseases
/ complications
Pedigree
Phenotype
RNA-Binding Proteins
/ genetics
White Matter
/ diagnostic imaging
Young Adult
AIMP1
Cerebral white matter
Epilepsy
N-acetylaspartate
Journal
Pediatric neurology
ISSN: 1873-5150
Titre abrégé: Pediatr Neurol
Pays: United States
ID NLM: 8508183
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
25
07
2018
revised:
05
09
2018
accepted:
22
09
2018
pubmed:
28
11
2018
medline:
24
3
2020
entrez:
28
11
2018
Statut:
ppublish
Résumé
Mutations in AIMP1, which plays an important role in the development and maintenance of axon-cytoskeleton integrity and regulating neurofilaments, cause neurodegeneration of variable severity and white matter abnormalities. From the patient records we analyzed the clinical evaluation, molecular genetics, neurodiagnostic, and neuroradiological investigations. We describe six members of a large consanguineous family with a phenotype of severe neurodegeneration in the form of developmental delays, progressive microcephaly, epilepsy, and failure to thrive. MRI showed callosal atrophy and T2 hyperintensity in the superficial white matter. The periventricular and deep white matter structures were, however, preserved. MR spectroscopy demonstrated N-acetylaspartate preservation without evidence of neuroinflammation. Exome sequencing showed a novel homozygous mutation of the AIMP1 gene in all individuals: c.917A>G (p.(Asp306Gly)). This novel homozygous mutation of the AIMP1 gene is characterized by preserved development of the periventricular and deep white matter structures as demonstrated by MRI and MR spectroscopy correlation.
Sections du résumé
BACKGROUND
Mutations in AIMP1, which plays an important role in the development and maintenance of axon-cytoskeleton integrity and regulating neurofilaments, cause neurodegeneration of variable severity and white matter abnormalities.
METHODS
From the patient records we analyzed the clinical evaluation, molecular genetics, neurodiagnostic, and neuroradiological investigations.
RESULTS
We describe six members of a large consanguineous family with a phenotype of severe neurodegeneration in the form of developmental delays, progressive microcephaly, epilepsy, and failure to thrive. MRI showed callosal atrophy and T2 hyperintensity in the superficial white matter. The periventricular and deep white matter structures were, however, preserved. MR spectroscopy demonstrated N-acetylaspartate preservation without evidence of neuroinflammation. Exome sequencing showed a novel homozygous mutation of the AIMP1 gene in all individuals: c.917A>G (p.(Asp306Gly)).
CONCLUSIONS
This novel homozygous mutation of the AIMP1 gene is characterized by preserved development of the periventricular and deep white matter structures as demonstrated by MRI and MR spectroscopy correlation.
Identifiants
pubmed: 30477741
pii: S0887-8994(18)30811-7
doi: 10.1016/j.pediatrneurol.2018.09.010
pii:
doi:
Substances chimiques
Cytokines
0
Neoplasm Proteins
0
RNA-Binding Proteins
0
small inducible cytokine subfamily E, member 1
0
Aspartic Acid
30KYC7MIAI
N-acetylaspartate
997-55-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
57-61Informations de copyright
Copyright © 2018. Published by Elsevier Inc.