Clinical phenotype and genotype analysis of hereditary spastic paraplegia type 35 / 中华神经科杂志

ABSTRACT

Objective:To report 8 cases of hereditary spastic paraplegia type 35 (SPG35) in Chinese mainland, summarize the clinical and genetic features of this disease.Methods:Eight probands with SPG35, admitted in Shanghai Jiao Tong University Affiliated Sixth People′s Hospital and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2006 to June 2021, were collected in detail. Physical examination, cranial imaging examination and whole exome sequencing were conducted, followed by Sanger sequencing and family co-segregation. In addition, the recent advances in clinical, genetic and pathogenesis studies of the disease were also reviewed.Results:Among all of the 8 patients, 7 had juvenile-onset and 1 was adult-onset. The clinical phenotype of 2 cases was pure spastic paraplegia. The other 6 cases presented with complicated form, which was characterized by not only motor dysfunction, but also cognitive impairment and dysphagia, etc. Genetic testing revealed a total of 13 fatty acid 2-hydroxylase (FA2H) gene (NM_024306) mutations, of which 6 were reported and 7 were newly reported in this study.Conclusions:SPG35 is an autosomal recessive neurodegenerative disease with highly phenotypic heterogeneity, with the causative gene as FA2H. The genotype-phenotype correlations in SPG35 are not clear.