Table 4.
PPMS patients who carry a reported phenocopy variant
| Clinical characteristics | Genetic Variant | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID | Sex | Age at onset | 2010 International Panel Criteria a | Gene | Disorder (inheritance) | Reported Variant b | Typec | Platform d | |||||
| Progressive course | Positive CSF (elevated IgG index, OCBs) | Brain MRI | Spine MRI | Gad + | Meets criteria | ||||||||
| 020069 | F | 37 | + | ND | + | + | − | + | KIF5A | SPG10 (AD) | p.A361V | mis | CGI |
| 041225 | F | 51 | + | + (+, +) | + | − | − | + | MLC1 | MLC (AR) | p.P92S | mis | CGI |
| 650008 | F | 50 | + | + (+, +) | + | + | − | + | REEP1 | SPG31 (AD) | c.606+43G>T | 3′ | CGI |
| 650084 | F | 48 | + | + (−, +) | + | + | − | + | SPG7 | SPG7 (AR,AD) | c.1552+1G>T | ss | MS chip |
| 700019 | F | 61 | + | + (+, +) | + | + | + | + | SPG7 | SPG7 (AR,AD) | p.A510V | mis | MS chip |
| 520139* | F | 26 | + | + | − | + | − | + | REEP1 | SPG31 (AD) | c.606+43G>T | 3′ | OA |
| 521859* | M | 57 | + | ND | + | ND | − | − | REEP1 | SPG31 (AD) | c.606+43G>T | 3′ | OA |
2010 International Panel Criteria includes (a) progression since onset without relapses, and (b) 2 of the following 3 criteria: positive CSF (elevated IgG index or oligoclonal bands), brain lesions consistent with MS, and spinal cord lesions consistent with MS. “+” denotes satisfies criteria, “-“ denotes does not satisfy criteria, “ND” denotes test was not done. GAD denotes gadolinium enhancement on at least one MRI brain or spinal cord.
“c.” denotes coding DNA sequence position. “p.” denotes protein amino acid position. Only the variant corresponding to the primary transcript according to ExAC is provided.
Variant types: mis=missense, ss=splice site, 3′=3′UTR
Genotyping platforms: CGI=WGS via Complete Genomics Inc, MS chip=MS replication chip, OA=OpenArray
PPMS patients from Phase 1 replication cohort. CSF for patient 520139, performed at the NIH in 1977, was reported to be consistent with MS, however results were not available.