Objective: To carry out a clinical and genetic study of a large Indian family emigrated in Italy with autosomal dominant hereditary spastic paraplegia (ADHSP).

Background: HSPs are a group of inherited neurological disorders characterized by progressive spastic paraparesis of the lower limbs. Mutations in the SPG5A/CYP7B1 gene cause the second most frequent AR type of HSP.

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

Results: We identified a new frameshift mutation in SPG5A/CYP7B1 in a large Indian pedigree from Maharashtra region with HSP and atypical clinical features. The genetic variation falls on exon 4. All 11 patients had only a single heterozygous mutation. The PCR-RFLP analyses confirmed that affected family members carry the mutation in SPG5A/CYP7B1 while the unaffected members did not. Atypical clinical characteristics of SPG5A, including mental retardation and thin corpus callosum, were observed in the family members.

Conclusion: To our knowledge, this is the first report of a mutation in SPG5A/CYP7B1 in Indian patients, which signifies that SPG5A-HSP occurs in various ethnic populations, including those in India. Moreover, we support the hypothesis that SPG5A investigation should not be restricted to ARHSP since our mutation suggests a dominant effect in a large family over three generations. Finally, the affected subjects have supplementary clinical characteristics generally associated with other forms of HSP (ie mental retardation, thin corpus callosum). Further analysis of the effect of SPG5A/CYP7B1 mutations may elucidate the underlying mechanism of these features.

References: Lo Giudice T, Lombardi F, Santorelli FM, Kawarai T, Orlacchio A: Hereditary spastic paraplegia: clinical-genetic characteristics and evolving molecular mechanisms. Experimental Neurology 2014, 261C: 518-539

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MDS Abstracts - https://www.mdsabstracts.org/abstract/hsp-spg5a-cyp7b1-unusual-clinical-and-genetic-characteristics-in-an-indian-family/