Case Report: Mutation in AIMP2/P38, the Scaffold for the Multi-Trna Synthetase Complex, and Association With Progressive Neurodevelopmental Disorders

被引:3
|
作者
Mazaheri, Mahta [1 ,2 ,3 ]
Yavari, Mahdie [3 ,4 ]
Zare Marzouni, Hadi [5 ]
Stufano, Angela [6 ,7 ]
Lovreglio, Piero [7 ]
S'Amore, Simona [8 ]
Jahantigh, Hamid Reza [6 ,7 ]
机构
[1] Shahid Sadoughi Univ Med Sci, Sch Med, Dept Med Genet, Yazd, Iran
[2] Shahid Sadoughi Univ Med Sci, Mother & Newborn Hlth Res Ctr, Yazd, Iran
[3] Dr Mazaheris Med Genet Lab, Yazd, Iran
[4] Univ Isfahan, Fac Sci & Biotechnol, Dept Cell & Mol Biol & Microbiol, Div Genet, Esfahan, Iran
[5] Birjand Univ Med Sci, Qaen Sch Nursing & Midwifery, Birjand, Iran
[6] Univ Bari Aldo Moro, Dept Vet Med, Bari, Italy
[7] Univ Bari, Sect Occupat Med, Interdisciplinary Dept Med, Bari, Italy
[8] Univ Cambridge, Dept Med, Cambridge, England
关键词
leukodystrophies; WES; AIMP2; P38; neurodevelopmental disorders; multi-tRNA synthetase complex; LEUKODYSTROPHIES; CLASSIFICATION; PERSPECTIVES;
D O I
10.3389/fgene.2022.816987
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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页数:6
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