Deep Intronic SVA_E Retrotransposition as a Novel Factor in Canavan Disease Pathogenesis.

ABSTRACT: Canavan disease (CD) is a rare autosomal recessive leukodystrophy caused by biallelic pathogenic variants in the ASPA gene. CD is characterized by developmental delay, macrocephaly, and abnormal muscle tone. The biochemical diagnosis is confirmed by increased N-acetylaspartic acid levels. The phenotypic presentation varies, with 85-90% of individuals exhibiting the severe, typical form, while 10-15% present with a milder, atypical form. Here we report on five patients with a clinical and biochemically proven diagnosis in whom a second pathogenic variant had not yet been identified. Targeted long-read sequencing of the entire ASPA gene revealed an SVA_E retrotransposable element located in intron 4 that had been missed by standard short-read-based diagnostic procedures.

SUBMITTER: Weiß M 

PROVIDER: S-EPMC12596875 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature