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A Novel Mutation in Hld-5 With a Comprehensive Literature Review Publisher



S Bayat SAHAR ; M Gholami MILAD ; H Khodadadi HAMIDREZA ; Mr Ghazavi Mohammad REZA ; J Nasiri JAFAR ; M Kheirollahi MAJID
Authors

Source: Basic and Clinical Neuroscience Published:2025


Abstract

Background: Hypomyelinating leukodystrophie-5 (HLD-5) is a rare multiple congenital anomaly with intellectual disability caused by an autosomal recessive mutation in the FAM126A gene and is characterized by bilateral congenital cataract, developmental delay, cerebellar ataxia, slowly progressive gait disturbance and cognitive impairment. This study aims to contribute to a better understanding of HLD-5 by reviewing previous patients and introducing a novel variant in a new case. Methods and Results: We subjected a case with an initial diagnosis of HLD-5 in an Iranian family. To identify the possible genetic cause(s), whole exome sequencing (WES) was carried out to detect exon mutations and Sanger sequencing was performed to verify the DNA sequence variants and co-segregation analysis. We predicted the potential deleterious effects of the novel mutation using in silico predictive tools. WES identified a novel homozygous mutation (NM_032581: c.636_639del p.C213Dfs*7) in the FAM126A gene. The variant can cause premature termination of amino acid translation or affect mRNA expression. Conclusions: In this study, the clinical manifestations and molecular findings of HLD-5 were explained. Additionally, we reported a novel variant and some rare clinical features, such as exophthalmos and strabismus, in our proband for the first time. Further research is needed to clarify the molecular mechanisms underlying HLD-5 pathogenesis. © 2025 Elsevier B.V., All rights reserved.
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