SPG11: clinical and genetic features of seven Czech patients and literature review

ABSTRACT

SPG11 is one of the most frequent autosomal recessively inherited types of hereditary spastic paraplegias (HSP or SPG). We describe the first seven patients from the Czech Republic with biallelic pathogenic variants in the SPG11. The typical HSP neurological findings are present in all the described patients in that the signs of a complicated phenotype develop slowly. The speed of disease progression, and the severity of gait impairment, was fast in all patients but the phenotype varied from patient to patient. Thin corpus callosum was not observed in two patients. Two Czech SPG11 patients had unusual late onset of disease and both were compound heterozygotes for the c.5381T>C variant. Therefore, we looked for a potential ralationship between the type of variant in the SPG11 gene and the age of disease onset. By reviewing all described SPG11 patients carrying at least one missense pathogenic variant in the SPG11 gene we did not found any relationship between the age of onset and the type of variant. Together twelve pathogenic variants, including gross deletions, were found in the SPG11 gene the Czech SPG11 patients, the c.3454-2A>G variant is novel.

KEYWORDS:

• SPG11
• adult onset
• the corpus callosum atrophy
• ´ears of the lynx´ sign
• missense variant

Acknowledgments

We would like to thank all the patients and their families for their willingness to participate in this study. Supported by: MEYS 8F20002 under the frame of EJP RD, the European Joint Programme on Rare Diseases. In addition, this project has received funding from the European Union’s Horizon 2020 research and innovation programme under the EJP RD COFUND-EJP N° 825575.

MV was supported by MH CZ – DRO, Motol University Hospital, Prague, Czech Republic 00064203, Institutional Support of Excellence 2. LF UK Grant No. 699012. MV, EV, RJ and JR are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the European Joint Programme on Rare Diseases [MEYS 8F20002]; Ministerstvo Zdravotnictví Ceské Republiky (CZ) [Grant No. 699012]; European Union’s Horizon 2020 research and innovation programme [EJP N° 825575].