Copy number variations in SPAST and ATL1 are rare among Brazilians

Copy number variations (CNV) may represent a significant proportion of SPG4 and SPG3A diagnosis, the most frequent autosomal dominant subtypes of hereditary spastic paraplegias (HSP). We aimed to assess the frequency of CNVs in SPAST and ATL1 and to update the molecular epidemiology of HSP families in southern Brazil. A cohort study that included 95 Brazilian index cases with clinical suspicion of HSP was conducted between April 2011 and September 2022. Multiplex Ligation Dependent Probe Amplification (MLPA) was performed in 41 cases without defined diagnosis by different massive parallel sequencing techniques (MPS). Diagnosis was obtained in 57/95 (60%) index cases, 15/57 (26.3%) being SPG4. Most frequent autosomal recessive HSP subtypes were SPG7 followed by SPG11, SPG76 and cerebrotendinous xanthomatosis. No CNVs in SPAST and ATL1 were found. Copy number variations are rare among SPG4 and SPG3A families in Brazil. Considering the possibility of CNVs detection by specific algorithms with MPS data, we consider that this is likely the most cost-effective approach to investigate CNVs in these genes in low-risk populations, with MLPA being reserved as an orthogonal confirmatory test.

Automated summary

This study aimed to evaluate the frequency of CNVs in SPAST and ATL1 genes and update the molecular epidemiology of HSP families in southern Brazil. The results showed that in 57 out of 95 index cases, a diagnosis was obtained, with 15 of them being SPG4. SPG7 was the most frequent autosomal recessive HSP subtype, followed by SPG11, SPG76, and cerebrotendinous xanthomatosis. No CNVs were found in SPAST and ATL1 genes, indicating their rarity among Brazilian SPG4 and SPG3A families. Considering specific algorithms with MPS data, CNVs detection is likely the most cost-effective approach in low-risk populations, with MLPA reserved as an orthogonal confirmatory test.