Abstract

Mutation analysis of four Chinese families with pure hereditary spastic paraplegia: pseudo- X-linked dominant inheritance and male lethality due to a novel ATL1 mutation

Author(s): N. Zhao, Y. Sui, X.F. Li, W. Liu, Y.P. Lu, W.H. Feng, C. Ma, Y.W. Wang, H.X. Bao, F. Huang, H. Wang, D.X. Yi, W.T. Han and M. Jiang

We studied four Chinese families with pure hereditary spastic paraplegia (HSP) to investigate the clinical features and associated genetic mutations. Linkage analysis was performed for all families to map the disease locus onto autosomal chromosomes, and related loci involved in HSP on the X chromosome were also examined. Polymerase chain reaction (PCR) sequencing was used to detect gene mutations. To confirm the influence of a splice-site mutation on mRNA, we used reverse transcription-PCR and direct sequencing. Linkage analysis and ATL1 gene sequencing of amniocytes were performed for prenatal genetic diagnosis. One missense variant (c.1517T>A) and a splice-site mutation (c.1245+1G>A) in SPAST, and two missense variants (c.715C>T, c.1204T>G) in ATL1 were identified.

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