Deep intronic SVA_E insertion identified as the most common pathogenic variant associated with Canavan disease: a diagnostic blind spot
Canavan disease is an autosomal recessive neurodegenerative disorder caused by biallelic pathogenic variants in the ASPA gene, leading to progressive and irreversible motor and cognitive decline. Short-read sequencing is traditionally used for genetic testing, but has often been unsuccessful for Canavan disease. The reason for this has now become clear — Canavan disease is thought to be caused by a large structural variant beyond the detection capabilities of short-read technologies. Using Oxford Nanopore sequencing, Dominguez Gonzalez and Bell et al. uncovered a retrotransposon insertion present in all eight research samples but missed by previous clinical tests. Upon searching population databases, they found that the variant exists in individuals from many different ancestries and could represent the most common pathogenic cause of Canavan disease.
Sample type: DNA from whole blood
