Background and aims: Paraplegin encoded by SPG7 causes autosomal recessive
hereditary spastic paraplegia (HSP). It is responsible for 5–12% of the HSPs. The
SPG7 mutations result in pure HSP, but based on some observations
the clinical picture can be more colourful.Methods: We screened 342 Hungarian
patients for damaging SPG7 rare variants (DRVs) by NGS. Based on phenotype
5 subcohort were established: spastic paraplegia; ataxia; motoneuron lesion;
progressive external ophthalmoplegia, and patient with mitochondrial
encephalopathy. We aimed to identify the frequency of the DRVs of the SPG7 in these
patients and to compare its ratio in the subgroups.Results: We identified 17 patients
with biallelic, 16 patients with monoallelic DRVs. The p.Leu78Ter mutation was
present in nine cases with biallelic, in four cases with monoallelic presentation.
This DRV seems to be the most common DRV associated with HSP7 in Hungary. In
patients with heterozygous presentation is seems to be disease-causing similarly
as the p.Ala510Val mutation, which was proposed previously to be associated
with HSP in heterozygous form as well. This latter was also common in the Hungarian
cohort. The ratio of DRVs was the following in the subgroups: spasticity 11,39%,
ataxia 17,61%, motoneuron lesion 7,87%, PEO 11,90%., and mitochondrial encephalopathy
9,64%.Conclusion: SPG7 mutation result in wide clinical phenotype.
The p.Leu78Ter DRV is the most common pathogenic mutation in Hungary beside
the p.Ala510Val. Both of these DRVs may result in clinical signs both
in monoallelic and biallelic form, the monoallelic alterations result in less severe
phenotype.Disclosure: The authors have nothing to declare.