Two types of recessive hereditary spastic paraplegia in Roma patients in compound heterozygous state; no ethnically prevalent variant found.

Hereditary spastic paraplegia (HSP or SPG) is a group of rare upper motor neuron diseases. As some ethnically-specific, disease-causing homozygous variants were described in the Czech Roma population, we hypotesised that some prevalent HSP-causing variant could exist in this population. Eight Czech Roma patients were found in a large group of Czech patients with suspected HSP and were tested using gene panel massively parallel sequencing (MPS). Two of the eight were diagnosed with SPG11 and SPG77, respectively. The SPG77 patient manifests a pure HSP phenotype, which is unusual for this SPG type. Both patients are compound heterozygotes for two different variants in the SPG11 (c.1603-1G>A and del ex. 16-18) and FARS2 (c.1082C>T and del ex.1-2) genes respectively; the three variants are novel. In order to find a potential ethnically-specific, disease-causing variant for HSP, we tested the heterozygote frequency of these variants among 130 anonymised DNA samples of Czech Roma individuals without clinical signs of HSP (HPS-negative). A novel deletion of ex.16-18 in the SPG11 gene was found in a heterozygous state in one individual in the HSP-negative group. Haplotype analysis showed that this individual and the patient with SPG11 shared the same haplotype. This supports the assumption that the identified SPG11 deletion could be a founder mutation in the Czech Roma population. In some Roma patients the disease may also be caused by two different biallelic pathogenic mutations.

First cases in the Czech Republic of the Hallervorden-Spatz disease resulting from mutation in the pantothenate kinase 2 gene.

Hallervorden-Spatz disease (HSD) was and is known as a rare disorder primarily characterized by progressive extrapyramidal dysfunction and dementia alongside optic nerve atrophy or retinal degeneration and pyramidal signs. The rate of occurence of HSD is thus far unknown. Progress in DNA diagnostics stirred up a nomenclature and from HSD, or, perhaps better put, the Hallervorden-Spatz syndrome, crystallized the pantothenate kinase-associated neurodegeneration (PKAN) as a clearly defined entity on the level of DNA. In this paper, we present our first results and experience in the diagnosis of PKAN in the Czech Republic and discuss questions related to differential diagnosis.