AIMP1 deficiency presents as a cortical neurodegenerative disease with infantile onset
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We report the second family with AIMP1 deficiency, due to a homozygous truncating AIMP1 (g.107248613 C > T) mutation. This female showed early-onset developmental arrest, intractable epileptic spasms, microcephaly, and a rapid clinical course leading to premature death, associated with cerebral atrophy and myelin deficiency on brain MRI. Clinical and neuroimaging findings are consistent with a primary neuronal degenerative disorder, rather than with the previously reported Perlizaeus-Merzbacher-like phenotype. Given its critical role in neurofilament assembly 16, impaired myelin formation is due to neuronal/axonal dysfunction. We propose that AIMP1 deficiency be added to the differential diagnosis of infantile onset, progressive neurodegenerative disease.
KeywordsSeizures Epilepsy Microcephaly Developmental delay Hypomyelination Cerebral atrophy Neuron Genomics
We gratefully acknowledge the family for their participation in this study, Dr. K. Selby and Dr. L. Cline for the clinical management of the patient, Mrs. X. Han for the Sanger sequencing, Mr. B. Sayson for consenting and data management, and Mrs. M. Higginson for DNA extraction and sample handling. The authors have no conflict of interest to declare.
The authors declare that the experiments comply with the current laws of Canada, the country in which they were performed.
This work was supported by funding from the B.C. Children’s Hospital Foundation as “1st Collaborative Area of Innovation” (www.tidebc.org), Genome BC (SOF-195 grant), and the Canadian Institutes of Health Research (#301221 grant), BC Clinical Genomics Network (#00031 grant).
Conflict of interest
The authors declare that they have no conflict(s) of interest.