Posted - December 2014 in Research Highlights
Large HSP study in China
Most HSP research finds no differences between the genders or due to ethnicity, but this large research study found that the incidence of HSP was 2.5 times higher in males than females in HSP affected families in the Hunan province of China. It also found that the rate of disease progression is significantly faster in males.
204 people (94 males and 110 females) from 22 families with at least one member in each known to have SPG4 HSP were clinically and genetically assessed. They found:
79 of the 204 had an SPG4 mutation (39%)
65 of the 79 with an SPG4 mutation showed symptoms while the other 14, almost 20%, did not
82% of those with an SPG4 mutation had pure HSP and 18% complicated
44 of the 94 males had an SPG4 mutation (47%), while just 21 of the 110 females did (19%)
Males also had significantly faster progression of the disease than females.
Background: 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.
Objective: The purpose of this study was to investigate the mutation frequencies and the clinical phenotypes of Chinese spastic paraplegia patients.
Methods: Direct sequencing and a multiplex ligation-dependent probe amplification assay were applied to detect the mutations of SPAST and ATL1 in 54 autosomal-dominanthereditary spastic paraplegia probands and 66 isolated cases. Next, mutations in NIPA1, KIF5A, REEP1 and SLC33A1 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.
Results: Altogether, 27 families were diagnosed as SPG4, 3 as SPG3A and 1 as SPG6. No mutations in KIF5A, REEP1 or SLC33A1 were found; 9 SPAST mutations were novel. There was no p.S44L or p.P45Q variant in SPAST and no p.G563A variant in HSPD1 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.
Conclusions: 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.
SOURCE: Neurodegener Dis. 2014 Oct 22. [Epub ahead of print] © 2014 S. Karger AG, Basel. PMID: 25341883
Mutation and Clinical Characteristics of Autosomal-Dominant Hereditary Spastic Paraplegias in China.
1Department of Neurology, Xianga Hospital of Central South University, Changsha, China.