A polymorphic AT-repeat causes frequent allele dropout for an MME mutational hotspot exon

Pathogenic variants in the MME gene cause dominant and recessive late onset axonal hereditary neuropathy. In this study, we identified that a short increase in an AT-repeat close to two MME mutations is a frequent cause of allele dropout during Sanger sequencing causing false interpretation of the results in several of the patients. This may result in an incorrect diagnosis, which has a considerable clinical impact for genetic counselling and prognosis. Although, NGS is frequently applied for routine diagnostics, Sanger sequencing is still used for verification and segregation analysis in a family. The fact that a small increase in a repetitive sequence may lead to amplification failure, is important to bear in mind when designing primers for Sanger sequencing. (By Dr. Helle Høyer, https://jmg.bmj.com/content/early/2022/03/22/jmedgenet-2021-108281 )

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