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Updated: Aug 8, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Novel missense mutation in ALS2 gene results in infantile ascending hereditary spastic paralysis
Eleonore Eymard-Pierre1, Koji Yamanaka, Martin Haeussler
1Institut National de la Sante et de la Recherche Médicale U384 and Human Genetics Department, CHU, Clermont-Ferrand, France.
Objective:
Recessive mutations in ALS2 (juvenile amyotrophic lateral sclerosis) are causative for early-onset upper motor neuron diseases, including infantile ascending hereditary spastic paralysis (IAHSP). The goal of this study is to identify novel disease-causing ALS2 mutations.
Methods:
Mutations in ALS2 were screened by direct sequencing of complementary DNA obtained from patients' lymphoblasts.
Results:
We report a novel ALS2 missense mutation in patients affected by IAHSP. This homozygous G669A mutation in exon 4 is predicted to result in a tyrosine substitution at cysteine 156 of the RCC1 (regulator of chromatin condensation)-like domain, encoding a putative guanine exchange factor for Ran guanosine triphosphatase, leading to a loss of ALS2 function due to instability of mutant protein.
Interpretation:
These results highlight the important role of the RCC1-like domain in ALS2 stability and function that is essential for upper motor neuron maintenance.
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