Table 1 Molecular analysis of gene mutations in SPG11
From: Chinese families with autosomal recessive hereditary spastic paraplegia caused by mutations in SPG11
Patient | Type | Location | Variant | SIFT/PolyPhen/MutTaster | ExAC Allele Frequency | Clinical Features | Predicted Amino Acid Change | Mutation Type | Pathogenicity class according to ACMG | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
Family 1 | compound heterozygous | Exon 33 | c.6284 T > Ca | Deleterious/deleterious/deleterious | 0.0097 | Spastic paraparesis, dysarthria, amyotrophy of the distal right hand muscles | p.(Leu2095Ser) | Missense | PM1 + PM2 + PM3 + PP3 + PP4 (likely pathogenic) | Kim, et al. |
Exon 6 | c.1203 delA | Unknown/unknown/ unknown | 0.00009 |  | p.(Lys401fs) | Frameshift | PVS1 + PS1 + PM2 + PM3 + PP4 (pathogenic) | Denora, et al. | ||
Family 2 | compound heterozygous | Intron24 | c.4162-10 T > G | Unknown/unknown/ unknown | 0 | Spastic cerebellar ataxic gait, intentional tremor of left hand, cognitive impairment | – | Missense | PM1 + PM2 + PM3 + PP4 (likely pathogenic) | Novel |
Exon11 | c.2163dupT | Unknown/unknown/ unknown | 0 |  | p. (Ile722fs) | Frameshift | PVS1 + PM2 + PM3 + PP4 (pathogenic) | Liao, et al. | ||
Family 3 | homozygous | Exon 4 | c.733_734del |  | 0 | Walking difficulties, spastic paraparesis, dysarthria, cognitive impairment | p. (Met245fs) | Frameshift | PVS1 + PS1 + PM2 + PP4 (pathogenic) | Stevanin, et al. |
Family 4 | homozygous | Exon 22 | c.3805dupA | Unknown/unknown/ unknown | 0 | Spastic paraparesis, limb pain, cognitive impairment | p.(Arg1269fs) | Frameshift | PVS1 + PM1 + PM2 + PP4 (pathogenic) | Novel |
Family 5 | compound heterozygous | Exon2 | c.317C > A | Deleterious/deleterious/benign | 0 | Walking difficulties, spastic paraparesis, tremor in the upper limbs, cognitive impairment | p. (Ala106Asp) | Missense | PM2 + PP1 + PP3 + PP4 (VUS) | Novel |
Intron20 | c.3520 + 3_3520 + 6del | Unknown/unknown/ unknown | 0 |  | – | Intron deletion | PM2 + PP1 + PP4 (VUS) | Novel | ||
Family 6 | homozygous | Exon 38 | c.6856C > T | Unknown/unknown/ deleterious | 0.0002 | Gait abnormality, spastic paraparesis, dysarthria, cognitive impairment | p.(Arg2286X) | Nonsense | PVS1 + PS1 + PM2 + PP4 (pathogenic) | Denora. et al. |
Family 7 | homozygous | Intron 39 | c.7151 + 4_7151 + 7delAGTA | Unknown/unknown/ unknown | 0 | Gait abnormality, spastic paraparesis, cognitive impairment | – | splicing | PS1 + PS3 + PM2 + PP4 (pathogenic) | Liao, et al. |
Family 8 | homozygous | Intron 21 | c.3686 + 3_3686 + 6delGAGT | Unknown/unknown/ unknown | 0 | Spastic paraparesis, cognitive impairment, walking difficulties | – | Frameshift | PM2 + PP4 (VUS) | Novel |
Family 9 | homozygous | Exon 7 | c.1561_1562delAA | Unknown/unknown/ unknown | 0 | Spastic cerebellar ataxic gait, cognitive impairment, urinary disturbances, dysarthria, dysphagia, distal amyotrophy of lower limbs | p.(Asn521Trpfs) | Frameshift | PVS1 + PM1 + PM2 + PP4 (pathogenic) | Novel |