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known mutations
SPG4 (Spastin): ~ 150
SPG3A (Atlastin): ~ 20
NIPA1: ~ 3
Research only: BSCL2
Hereditary spastic paraplegia –Gene testing
79 patients tested
Identification rate in Molecular Medicine laboratory:
SPG4 (Spastin) 24%
SPG3A (Atlastin) < 1%
NIPA1 -
Hereditary spastic paraplegia –Genes
Missense Mutation
Nonsense Mutation
Small Insertion/Deletion Mutation
Insertion/Deletion of large DNA fragments
Hereditary spastic paraplegia – Mutations
Normal gga agt gac cta acaG S D L T
Mutated gga agt aac cta acaG S N L T
Normal ggt cct atc cga gaaG P I R E
Mutated ggt cct atc tga gaaG P I stop
c.1684C>T p.R562X
truncated, non functionalprotein
c.1642G>A p.D548N
non functional protein
Normal atc aaa cgg gta tat gtg tct tta cca aat gag gag I K R V Y V S L P N E E
Mutated atc aaa ccg ggt ata tgt gtc ttt acc aaa tga ggaI K P G I C V F T K stop
c.1507-1508insC p.R503fsX511
truncated, non functionalprotein
no. of detected mutation
Missense Mutation 5
Nonsense Mutation 3
Small Insertion/Deletion Mutation 3
Insertion/Deletion of large DNA fragments 3
14
Hereditary spastic paraplegia – Mutations
DNA Scanning
Spastin & Atlastin
1. High Resolution Melt (HRM) –Missense, Nonsense, small insertion, small deletion
2. DNA sequencing3. Multiplex Ligation-dependent Probe Amplification (MPLPA) –
Exon duplication, Exon deletion
NIPA1
1. High Resolution Melt (HRM) –Missense, Nonsense, small insertion, small deletion
Known mutations in Spastin, Atlastin & NIPA1
1. DNA sequencing
Hereditary spastic paraplegia –Mutation discovery
Number ofknown mutations 10 2 2 - 16 5 6 12 10 11 16 12 7 7 11 7 7
Exon no. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
14 mutations idendified: 9 previously described5 new
SPG4 (Spastin): ~ 150 known mutations
Hereditary spastic paraplegia –Genes & Mutations
Exon no. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Number ofidentified mutations
in Mol Med lab 1 1 - - - 1 - 1 1 - 1 1 2 1 2 1 -
found in 2 unrelated individuals
3 large deletions idendified
SPG4 (Spastin): ~ 150 known mutations
Hereditary spastic paraplegia –Genes & Mutations
Exon no. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
SPG3A (Atlastin): ~ 20 known mutations
1 undescribed mutation identified
NIPA1: ~ 3 known mutations
no mutation
Hereditary spastic paraplegia –Genes & Mutations
