Case Report: Mutation in AIMP2/P38, the Scaffold for the Multi-Trna Synthetase Complex, and Association With Progressive Neurodevelopmental Disorders
Authors
Mazaheri, Mahta
Yavari, Mahdie
Zare Marzouni, Hadi
Stufano, Angela
Lovreglio, Piero
S'Amore, Simona
Jahantigh, Hamid Reza
Publication Date
2022-01-24Journal Title
Frontiers in Genetics
Publisher
Frontiers Media S.A.
Volume
13
Language
en
Type
Other
This Version
VoR
Metadata
Show full item recordCitation
Mazaheri, M., Yavari, M., Zare Marzouni, H., Stufano, A., Lovreglio, P., S'Amore, S., & Jahantigh, H. R. (2022). Case Report: Mutation in AIMP2/P38, the Scaffold for the Multi-Trna Synthetase Complex, and Association With Progressive Neurodevelopmental Disorders. [Other]. https://doi.org/10.3389/fgene.2022.816987
Abstract
Background: Leukodystrophies constitute a heterogeneous group of inherited disorders primarily affecting the white matter of the central nervous system. Aminoacyl-tRNA synthetases (ARSs) catalyze the attachment of an amino acids to their cognate transfer RNAs (tRNAs). Pathogenic variants in both cytosolic and mitochondrial ARSs have been linked to a broad range of neurological disorders, including hypomyelinating leukodystrophies and pontocerebellar hypoplasias (PCH). Aminoacyl tRNA synthetase-interacting multifunctional protein 2 (AIMP2), one of the three non-catalytic components of multi ARS complex, harbors anti-proliferative activity and functions as a proapoptotic factor thus promoting cell death. We report a case of a 7-month-old infant with a complex clinical presentation, including weight loss, severe anemia, skeletal abnormalities, microcephaly and MR imaging features of leukodystrophy with a novel mutation in AIMP2. Methods: Whole-exome sequencing (WES) was performed on the proband. Parental samples were analyzed by PCR amplification and Sanger sequencing. Results: Whole-exome sequencing revealed a novel variant c.A463T in the homozygous state in exon 3 (NM_001,326,607) of AIMP2 [p.(K155X)] in the proband. Parental carrier status was confirmed by target sequencing. Conclusion: Here, we present an Iranian case with leukodystrophy with a novel AIMP2 mutation. This finding broadens the mutational and phenotypic spectra of AIMP2-related leukodystrophy and offers guidance for proper genetic counselling for pre- and post-natal screenings as well as for disease management.
Keywords
Genetics, leukodystrophies, WES, AIMP2/P38, neurodevelopmental disorders, multi-tRNA synthetase complex
Identifiers
816987
External DOI: https://doi.org/10.3389/fgene.2022.816987
This record's DOI: https://doi.org/10.17863/CAM.81128
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.