Supplementary Material for: Mutation and Clinical Characteristics of Autosomal-Dominant Hereditary Spastic Paraplegias in China

<b><i>Background:</i></b> Hereditary spastic paraplegias constitute a heterogeneous group of inherited neurodegenerative disorders. To date, there has been no systematic mutation and clinical analysis for a large group of autosomal-dominant hereditary spastic paraplegias in China. <b><i>Objective:</i></b> The purpose of this study was to investigate the mutation frequencies and the clinical phenotypes of Chinese spastic paraplegia patients. <b><i>Methods:</i></b> Direct sequencing and a multiplex ligation-dependent probe amplification assay were applied to detect the mutations of <i>SPAST</i> and <i>ATL1</i> in 54 autosomal-dominant hereditary spastic paraplegia probands and 66 isolated cases. Next, mutations in <i>NIPA1</i>, <i>KIF5A</i>, <i>REEP1</i> and <i>SLC33A1</i> were detected in the negative patients. Subsets of spastic paraplegia patients were genotyped for the modifying variants. Further, detailed clinical data regarding the genetically diagnosed families were analysed. <b><i>Results:</i></b> Altogether, 27 families were diagnosed as SPG4, 3 as SPG3A and 1 as SPG6. No mutations in <i>KIF5A</i>, <i>REEP1</i> or <i>SLC33A1 </i>were found; 9 <i>SPAST</i> mutations were novel. There was no p.S44L or p.P45Q variant in <i>SPAST</i> and no p.G563A variant in<i> HSPD1</i> in either the 120 spastic paraplegia patients or the 500 controls. There was a remarkable clinical difference between the SPG4 and non-SPG4 patients and even between genders among the SPG4 patients. Non-penetrance and remarkable gender difference were observed in some SPG4 and SPG3A families. <b><i>Conclusions:</i></b> Our data confirm that hereditary spastic paraplegias in China represent a heterogeneous group of genetic neurodegenerative disorders in autosomal-dominant and apparently sporadic forms. Novel genotype-phenotype correlations were established.