Unveiling a novel AIMP2 c.157 C>T variant in a Moroccan patient with hypomyelinating leukodystrophy type 17: A case report and insights from a literature review

Hypomyelinating Leukodystrophy Type 17 is a rare autosomal recessive neurodevelopmental disorder characterized by defective myelin formation and progressive neurological impairment. We report the first genetically confirmed case of HLD17 in Africa, associated with a homozygous AIMP2 (NM_006303.4): c.157 C>T [p.(Gln53Ter)] nonsense mutation. This variant is predicted to result in a truncated protein, likely impairing the function of the multi-tRNA synthetase complex. A review of the literature was conducted using PubMed, ScienceDirect, and the Cochrane Library, retrieving two articles reporting four cases of HLD17. The clinical phenotype of HLD17 shows a consistent set of features in all genetically confirmed cases (6/6), including absent speech, severe global developmental delay, microcephaly, and growth impairment. Feeding difficulties, inability to walk, intellectual disability, and seizures were reported in all evaluable cases (5/5). Spasticity was seen in 5 of 6 cases. Less common findings include kyphoscoliosis (3/5), hirsutism (3/3), hyperreflexia (3/3), and flexion contractures (2/4). Craniofacial anomalies such as anteverted nares and mandibular prognathia are rare, reported in only 1 of 3 or 4 cases, respectively. The disorder typically begins in infancy. Neurophysiological and neuroimaging abnormalities, such as cerebral and cerebellar atrophy, suggest visual pathway involvement and a progressive neurodegenerative course. All reported HLD17 cases carry biallelic pathogenic nonsense AIMP2 variants predicted to cause loss of function; frameshift, splice site, and missense variants have not been reported in affected patients in the literature. This study contributes new insights into the clinical, neuroimaging, and genetic features of HLD17 for accurate diagnosis and better management.