Surreal illustration of a brain highlighting deep white matter and genetic connections.

Decoding AIMP1 Mutations: How a Rare Genetic Mutation Sheds Light on Neurodevelopment

Mira Elwood in Health & Wellness November 2025 • 4 min read.

"Unraveling the complexities of a novel homozygous AIMP1 mutation and its subtle yet significant impact on neuroimaging and deep white matter preservation."

The human body is a complex tapestry woven from threads of genes, each playing a crucial role in our development and overall health. Among these genes, AIMP1 stands out for its involvement in essential cellular processes. Recent studies have focused on mutations within this gene and their surprising effects, particularly on brain development and function. This article delves into a specific discovery: a novel homozygous mutation of the AIMP1 gene and its associated milder neuroimaging phenotype, characterized by the preservation of deep white matter in the brain.

AIMP1, or Aminoacyl-tRNA Synthetase Interacting Multifunctional Protein 1, is a critical component of the multi-tRNA synthetase complex. This complex, comprised of nine catalytic and three non-catalytic proteins (AIMP1/p43, AIMP2/p38, and AIMP3/p18), is fundamental in various signaling pathways and functional protein synthesis. The AIMP1 protein itself is multifunctional, exhibiting both cytokine and tRNA-binding activities, highlighting its diverse roles within the cell.

While AIMP1's importance is well-established, mutations in this gene have been linked to neurodegeneration and leukoencephalopathy. Previous research has documented severe cases, such as those reported by Feinstein et al., where affected individuals experienced rapid hypomyelination, severe developmental delays, and intellectual disabilities. However, a recent study sheds light on a milder presentation of AIMP1 mutation, offering new insights into the spectrum of effects this gene can have on neurological development.

What This AIMP1 Mutation Reveals About Brain Development

Surreal illustration of a brain highlighting deep white matter and genetic connections.

A recent study, led by researchers Ahmed BoAli, Kalthoum Tlili-Graiess, and colleagues, investigated six members of a large consanguineous family who presented with developmental delays, progressive microcephaly, epilepsy, and failure to thrive. Through detailed clinical evaluations, molecular genetics analyses, and neuroimaging studies, the researchers uncovered a novel homozygous mutation in the AIMP1 gene: c.917A>G (p.(Asp306Gly)).

This particular mutation distinguishes itself from previously documented severe cases through its milder neuroimaging phenotype. While patients exhibited callosal atrophy and T2 hyperintensity in the superficial white matter, the periventricular and deep white matter structures remained remarkably preserved. This preservation is a key finding, offering new insights into how AIMP1 mutations can manifest differently.

Clinical Presentation: Patients showed developmental delays, progressive microcephaly, epilepsy, and failure to thrive.
Neuroimaging: Callosal atrophy and T2 hyperintensity in superficial white matter were observed, but deep white matter was preserved.
Genetic Findings: A novel homozygous mutation c.917A>G (p.(Asp306Gly)) was identified in all affected individuals.

Magnetic resonance (MR) spectroscopy further supported these findings, demonstrating N-acetylaspartate preservation without evidence of neuroinflammation. This suggests that the mutation does not necessarily lead to widespread inflammation or severe metabolic disturbances in the brain, as seen in more severe cases. The researchers emphasized that the preserved development of periventricular and deep white matter structures is a hallmark of this specific mutation.

Implications and Future Directions

This research not only expands our understanding of AIMP1-related disorders but also highlights the complex relationship between genotype and phenotype in neurological conditions. Identifying this milder phenotype allows for more accurate diagnoses and potentially tailored interventions for affected individuals. By recognizing the specific neuroimaging characteristics associated with this mutation, clinicians can better predict the course of the disorder and provide appropriate support and management strategies.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.pediatrneurol.2018.09.010, Alternate LINK

Title: Novel Homozygous Mutation Of The Aimp1 Gene: A Milder Neuroimaging Phenotype With Preservation Of The Deep White Matter

Subject: Neurology (clinical)

Journal: Pediatric Neurology

Publisher: Elsevier BV

Authors: Ahmed Boali, Kalthoum Tlili-Graiess, Amal Alhashem, Saad Alshahwan, Giulio Zuccoli, Brahim Tabarki

Published: 2019-02-01

Everything You Need To Know

What exactly is AIMP1, and what role does it play in the body?

AIMP1, or Aminoacyl-tRNA Synthetase Interacting Multifunctional Protein 1, is a crucial component of the multi-tRNA synthetase complex, which includes nine catalytic and three non-catalytic proteins (AIMP1/p43, AIMP2/p38, and AIMP3/p18). Its key function is in functional protein synthesis. AIMP1 exhibits both cytokine and tRNA-binding activities, which underscores its multifaceted role within cells and contributes significantly to essential cellular processes.

What was the key finding in the research regarding the novel homozygous AIMP1 mutation?

The study, led by researchers Ahmed BoAli, Kalthoum Tlili-Graiess, and colleagues, identified a novel homozygous mutation in the AIMP1 gene, specifically c.917A>G (p.(Asp306Gly)), within a family exhibiting developmental delays, progressive microcephaly, epilepsy, and failure to thrive. This discovery highlights that AIMP1 mutations can present with varying degrees of severity, as this particular mutation showcases a milder neuroimaging phenotype compared to previously documented severe cases.

How does the neuroimaging phenotype associated with this specific AIMP1 mutation differ from that of previously documented, more severe cases?

This AIMP1 mutation, c.917A>G (p.(Asp306Gly)), is notable because, unlike more severe AIMP1 mutations that cause rapid hypomyelination, severe developmental delays, and intellectual disabilities, this mutation presents with callosal atrophy and T2 hyperintensity in the superficial white matter, while remarkably preserving the periventricular and deep white matter structures. MR spectroscopy further confirmed N-acetylaspartate preservation without neuroinflammation. This suggests different mutations can lead to a range of impacts on brain development.

What neuroimaging characteristics, beyond deep white matter preservation, are associated with the AIMP1 mutation c.917A>G (p.(Asp306Gly))?

The preservation of deep white matter, along with the presence of callosal atrophy and T2 hyperintensity in the superficial white matter, are key indicators in this specific presentation of AIMP1 mutation c.917A>G (p.(Asp306Gly)). Further, MR spectroscopy showing N-acetylaspartate preservation without neuroinflammation further supports these findings. Clinicians can use these neuroimaging characteristics to aid in the diagnosis and prediction of the disorder's progression, as well as implement appropriate support and management strategies.

What are the broader implications of identifying this milder AIMP1 mutation for understanding and treating neurological conditions, and what future research directions might this discovery inspire?

The identification of this milder AIMP1 mutation phenotype broadens our understanding of AIMP1-related disorders and the complex relationship between genotype and phenotype in neurological conditions. It paves the way for tailored diagnostic and therapeutic strategies and helps in predicting the disorder's course for affected individuals. Future research might focus on understanding why this specific AIMP1 mutation leads to a milder presentation compared to others and explore potential therapeutic interventions targeting the AIMP1 pathway to mitigate neurological symptoms.