Objective: To perform a clinical and genetic analysis of a large Ukrainian pedigree emigrated in Italy with autosomal recessive hereditary spastic paraplegia (ARHSP).

Background: HSPs are a class of hereditary neurological conditions distinguished by progressive spastic paraparesis of the lower extremities. Mutations in the SPG11/KIAA1840 gene produce the most common AR type of HSP.

Method: DNA extraction from lymphocytes, NGS analysis, direct sequencing of genomic DNA, RFLP test, clinical evaluation.

Results: We discovered a new homozygous spatacsin truncating mutation in SPG11/KIAA1840 in a large Ukrainian family emigrated in Italy with ARHSP and unusual clinical features. The genetic variation is on exon 7. All six affected family members had the homozygous mutation. The PCR-RFLP analyses confirmed that patients have the mutation in SPG11/KIAA1840 while the unaffected members did not. Abnormal clinical attributes of SPG11, including penile lichen sclerosus, were observed in the affected family members.

Conclusion: To our knowledge, this is the first description of a mutation in SPG11/KIAA1840 in Ukrainian patients, which signifies that SPG11-HSP appears in various ethnic populations, including those in Ukraine. Moreover, the affected subjects have supplementary clinical characteristics (penile lichen sclerosus). Additional analysis of the impact of SPG11/KIAA1840 mutations may clarify the basic mechanism of these features.

References: Meyyazhagan A, Orlacchio A: Hereditary spastic paraplegia: an update. International Journal of Molecular Sciences 2022, 23(3), 1697

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-genetic-research-in-a-large-ukrainian-family-with-autosomal-recessive-hereditary-spastic-paraplegia/