Author:
Mazaheri Mahta,Yavari Mahdie,Zare Marzouni Hadi,Stufano Angela,Lovreglio Piero,D'Amore Simona,Jahantigh Hamid Reza
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.
Subject
Genetics (clinical),Genetics,Molecular Medicine
Reference21 articles.
1. Pathogenic Variants in AIMP1 Cause Pontocerebellar Hypoplasia;Accogli;Neurogenetics,2019
2. Childhood Leukodystrophies: a Literature Review of Updates on New Definitions, Classification, Diagnostic Approach and Management;Ashrafi;Brain Dev.,2017
3. An Update on Clinical, Pathological, Diagnostic, and Therapeutic Perspectives of Childhood Leukodystrophies;Ashrafi;Expert Rev. Neurother.,2020
4. The burden of Inherited Leukodystrophies in Children;Bonkowsky;Neurology,2010
5. Whole-exome Enrichment with the Agilent Sureselect Human All Exon Platform;Chen;Cold Spring Harb. Protoc.,2015
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献