Genetic work-up of hereditary spastic paraplegias is crucial for classifying these disorders

Abstract

Dear Editor, We read, with interest, the article by Ortega et al. about the study of 35 Brazilian patients with hereditary spastic paraplegia (HSP), of whom 12 presented with a pure form of HSP and 23 with a complex form 1. We have the following comments and concerns. The main shortcomings of the study are that the trait of inheritance could be determined in only 5/12 of the pure HSPs and in only 8/23 of the complex forms, and that no genetic investigations were carried out in the 35 included patients 1. Since the most common of the autosomal dominant forms are SGP4, SPG3A, SPG31, and SPG10 in Europe and the Americas 2 , the 12 patients with a pure from should be tested for mutations in the SPAST, ATL1, REEP1, and KIF5A genes respectively. Since the most frequent of the autosomal recessive forms are the SPG11, SPG15, SPG7, and SPG5 in the Americas 2 , the 23 patients with a complex form should thus be tested for mutations in the SPG11, ZFYVE26, SPG7, and CYP7B1 genes, respectively. Not only should the index case be genetically screened, but also symptomatic and asymptomatic first-degree relatives. This is not only important for genetic counseling but also for assessing the prognosis in these patients. We do not agree with the statement that currently "over 70 distinct loci and over 50 genes have been identified" 1. According to a recent review by Roeben et al., currently at least 79 loci and at least 60 HSP genes have been identified 3 and the number of loci and causative genes is still increasing.

Reply

“…Dear Editor, We thank Finsterer et al 1 for their interest in our paper. However, we think that their concerns have missed the target.…”