Case Report
CAPN1 Variants as Cause of Hereditary Spastic Paraplegia Type 76
Table 1
Clinical and genetical characteristics of SPG76 cases reported in the literature.
| | Ethnicity | Age at onset | Age at diagnosis | Gender | Lower limbs spasticity | Upper limbs spasticity | Ataxia | Dysarthria | Oculomotor Impairment | Exon or Intron affected | Mutation | Type | Heterozygous /Homozygous | Consanguinity | Brain MRI | NCS and SSEP |
| 1 | Latin American | NA | NA | NA | + | + | - | - | - | - | c.1176G>A p.Trp392∗ | Stop gain mutation | Homozygous | + | NA | NA |
| 2 | Latin American | NA | NA | NA | + | + | - | - | - | - | c.1176G>A p.Trp392∗ | NA | Homozygous | + | NA | NA |
| 3 | Latin American | NA | NA | NA | + | + | - | - | - | - | c.1176G>A p.Trp392∗ | NA | Homozygous | + | NA | NA |
| 4 | Latin American | 22 | 37 | F | + | + | - | - | - | - | c.1176G>A p.Trp392∗ | NA | Homozygous | - | NA | NA |
| 5 | Caucasian | 20 | 46 | F | + | + | + | - | - | - | c.675C>A p.Tyr225∗ | Novel LoF Mutation | Homozygous | - | NA | NA |
| 6 | Caucasian | 35 | 51 | M | + | + | + | - | - | - | c.675C>A p.Tyr225∗ | Novel LoF Mutation | Homozygous | - | NA | NA |
| 7 | Latin American | 30 | 42 | F | + | + | + | - | - | - | c.1176G>A p.Trp392∗ c.618_619delAG p.Gly208Glnfs∗7 | LoF Mutation | Heterozygous | + | NA | NA |
| 8 | Latin American | 38 | - | M | + | + | + | - | - | - | c.1176G>A p.Trp392∗ | LoF Mutation | Homozygous | + | NA | NA |
| 9 | Arab | 20 | 31 | F | + | + | - | + | - | Ex:8 | c.884G>C p.Arg295Pro | LoF Mutation | Homozygous | + | NA | Normal |
| 10 | Arab | NA | NA | NA | NA | NA | NA | NA | NA | Ex:8 | c.884G>C p.Arg295Pro | LoF Mutation | Homozygous | + | NA | NA |
| 11 | Arab | NA | NA | NA | NA | NA | NA | NA | NA | Ex:8 | c.884G>C p.Arg295Pro | LoF Mutation | Homozygous | + | NA | NA |
| 12 | Arab | 35 | 47 | M | + | + | - | + | - | Ex:14 | c.1579C>T p.Gln527 | Stop variant | Homozygous | + | NA | Moderate Sensory Axonal Neuropathy |
| 13 | Arab | 36 | 44 | F | + | + | + | + | - | Ex:14 | c.1579C>T p.Gln527 | Stop variant | Homozygous | + | NA | Moderate Sensory Axonal Neuropathy |
| 14 | Arab | 22 | 42 | M | + | + | - | + | - | Ex:14 | c.1579C>T p.Gln527 | Stop variant | Homozygous | + | Normal | NA |
| 15 | Arab | 39 | 40 | M | + | + | + | + | - | Ex:14 | c.1579C>T p.Gln527 | Stop variant | Homozygous | + | NA | NA |
| 16 | Arab | NA | NA | NA | NA | NA | NA | NA | NA | Ex:14 | c.1579C>T p.Gln527 | Stop variant | Homozygous | + | NA | NA |
| 17 | Arab | NA | NA | NA | NA | NA | NA | NA | NA | Ex:14 | c.1579C>T p.Gln527 | Stop variant | Homozygous | + | NA | NA |
| 18 | Arab | NA | NA | NA | NA | NA | NA | NA | NA | Ex:14 | c.1579C>T p.Gln527 | Stop variant | Homozygous | + | NA | NA |
| 19 | Caucasian | 24 | 30 | F | + | - | - | - | - | Ex:4 | c.406delC p.Pro136Argfs∗40 | Deletion | Heterozygous | - | NA | Normal |
| 20 | Caucasian | 33 | 35 | M | + | - | - | - | - | Ex:4 | c.406delC p.Pro136Argfs∗40 | Deletion | Heterozygous | - | Atrophy of spinal cord | NA |
| 21 | Caucasian | 19 | 22 | F | + | + | + | - | - | Ex:4 | c.1605+5G>A | Mutation Splicing | Heterozygous | - | Normal | NA |
| 22 | Indian | 33 | 43 | F | + | + | + | + | - | Ex:3 | c.337+1G>A | Splice Mutation | Homozygous | + | Mild cerebellar atrophy | Normal |
| 23 | Indian | NA | NA | F | NA | NA | NA | NA | NA | Ex:3 | c.337+1G>A | Splice Mutation | Homozygous | + | NA | NA |
| 24 | Caucasian | 29 | 39 | F | + | + | + | + | + | Ex:6 | c.759+1G>A | Donor splice site | Homozygous | + | Mild cerebellar vermal atrophy | NA |
| 25 | Caucasian | 33 | 37 | F | + | + | + | + | - | Ex:6 | c.759+1G>A | Donor splice site | Homozygous | + | NA | NA |
| 26 | Caucasian | 5 | 16 | M | + | - | - | - | - | - | c.221GNA/ p.(G74D) c.911CNT/ p.(T304M) c.1418GNT/ p.(R473L) | missense | Heterozygous | - | Normal | Normal |
| 27 | Arab | 21 | 37 | F | + | + | + | + | - | - | c.994G>A P.Gly.332Arg | NA | Homozygous | + | Normal | Normal |
| 28 | Arab | 30 | 54 | F | + | + | + | + | - | Ex10 | c. 1176G>A p. Trp392 | Nucleotide substitution | Heterozygous | + | Normal | Normal |
| 29 | Arab | 15 | 30 | F | + | + | + | + | - | Ex:10 | c. 1176G>A p. Trp392 | Nucleotide substitution | Heterozygous | + | Normal | Normal |
| 30 | Asian | 37 | 42 | F | + | + | + | - | - | - | c.2118+1G>T | Donor Splice site | Homozygous | NA | NA | NA |
| 31 | Caucasian | 23 | 23 | M | + | - | - | - | - | - | c.397C>T | NA | Homozygous | + | NA | NA |
| 32 | Caucasian | 20 | 20 | F | + | - | - | - | - | - | c.397C>T | Mutation in DYSF | Homozygous | + | NA | NA |
| 33 | Asian | 37 | 37 | M | + | + | + | - | - | - | c.843+1G>C | Donor Splice Site | Homozygous | + | NA | NA |
| 34 | Caucasian | 13 | 14 | F | + | + | + | - | - | Ex: 13 | c.1534C>T p.Arg512Cys | NA | Homozygous | - | Small midbrain and ponds, cerebellar atrophy | Delayed cortical wave defective conduction of large sensory fibers |
| 35 (our case) | Latin American | 23 | 38 | F | + | + | + | + | + | In: 12 and 16 | c.1729+1G>A c.1353+2T>C | Donor Splice Mutation | Heterozygous | NA | Normal | NA |
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Abbreviations. F: female, M: male, +: present, -: absent, LoF: loss of function, DYSF: dysferlin, MRI: magnetic resonance image, C: cerebral, S: spinal, NCS: nerve conduction studies, SSEP: somatosensory evoked potentials, NA: not available.
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