Table 1.

Molecular Genetic Testing Used in Childhood Ataxia with Central Nervous System Hypomyelination / Vanishing White Matter (CACH/VWM)

Gene 1, 2Proportion of CACH/VWM Attributed to Pathogenic Variants in Gene 3Proportion of Pathogenic Variants 4 Detectable by Method
Sequence analysis 5Gene-targeted deletion/duplication analysis 6
EIF2B1 1.7% 39/9 7, 8, 9None reported
EIF2B2 16.6% 3>99%% 7See footnote 10.
EIF2B3 7.8% 322/22 7, 9, 11None reported
EIF2B4 7.4% 331/31 7, 9, 10None reported
EIF2B5 66.5% 3>99% 7None reported

Genes are listed in alphabetic order.


All or almost all individuals with CACH/VWM have biallelic pathogenic variants identified in one of the five associated genes [Maletkovic et al 2008, van der Knaap et al 2010, Hamilton et al 2018].


See Molecular Genetics for information on allelic variants detected in this gene.


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.


This number reflects the number of unique variants reported. Some variants are recurrent (see Molecular Genetics).


A single multigene deletion including EIF2B2 has been reported [Shimada et al 2012].


From: Childhood Ataxia with Central Nervous System Hypomyelination / Vanishing White Matter

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