known mutations

1
Hereditary spastic paraplegia Gene testing
known mutations SPG4 (Spastin) 150 SPG3A
(Atlastin) 20 NIPA1 3 Research only
BSCL2
2
Hereditary spastic paraplegia Genes
79 patients tested Identification rate in
Molecular Medicine laboratory SPG4
(Spastin) 24 SPG3A (Atlastin) lt
1 NIPA1 -
3
Hereditary spastic paraplegia Mutations
Missense Mutation           Nonsense
Mutation Small Insertion/Deletion Mutation
Insertion/Deletion of large DNA fragments
Normal gga agt gac cta aca G S D L T
Mutated gga agt aac cta aca G S N L
T

• c.1642GgtA p.D548N
• non functional protein

Normal ggt cct atc cga gaa G P I R
E Mutated ggt cct atc tga gaa G P I
stop

• c.1684CgtT p.R562X
• truncated, 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 gga I K P G I
C V F T K stop

• c.1507-1508insC p.R503fsX511
• truncated, non functional
• protein

4
Hereditary spastic paraplegia Mutations
no. of detected mutation Missense
Mutation 5       Nonsense Mutation
3 Small Insertion/Deletion Mutation 3
Insertion/Deletion of large DNA fragments
3 14
5
Hereditary spastic paraplegia Mutation discovery

• DNA Scanning
• Spastin Atlastin
• High Resolution Melt (HRM)
• Missense, Nonsense, small insertion, small
  deletion
• 2. DNA sequencing
• 3. Multiplex Ligation-dependent Probe
  Amplification (MPLPA)
• Exon duplication, Exon deletion
• NIPA1
• High Resolution Melt (HRM)
• Missense, Nonsense, small insertion, small
  deletion
• Known mutations in Spastin, Atlastin NIPA1
• 1. DNA sequencing

6
Hereditary spastic paraplegia Genes Mutations
SPG4 (Spastin) 150 known mutations
1 2 3 4 5 6 7
8 9 10 11 12 13 14 15 16
17
1 2 3 4 5 6 7
8 9 10 11 12 13 14 15 16
17
Exon no.
Exon no.
Number of identified mutations in Mol Med lab
1 1 - - - 1
- 1 1 - 1 1 2 1
2 1 -
found in 2 unrelated individuals
14 mutations idendified 9 previously
described 5 new
7
Hereditary spastic paraplegia Genes Mutations
SPG4 (Spastin) 150 known mutations
Exon no.
1 2 3 4 5 6 7
8 9 10 11 12 13 14 15 16
17
3 large deletions idendified
8
Hereditary spastic paraplegia Genes Mutations
SPG3A (Atlastin) 20 known mutations 1
undescribed mutation identified NIPA1 3
known mutations no mutation