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Table 1 Molecular analysis of gene mutations in SPG11

From: Chinese families with autosomal recessive hereditary spastic paraplegia caused by mutations in SPG11

PatientTypeLocationVariantSIFT/PolyPhen/MutTasterExAC Allele FrequencyClinical FeaturesPredicted Amino Acid ChangeMutation TypePathogenicity class according to ACMGReference
Family 1compound heterozygousExon 33c.6284 T > CaDeleterious/deleterious/deleterious0.0097Spastic paraparesis, dysarthria, amyotrophy of the distal right hand musclesp.(Leu2095Ser)MissensePM1 + PM2 + PM3 + PP3 + PP4 (likely pathogenic)Kim, et al.
Exon 6c.1203 delAUnknown/unknown/ unknown0.00009 p.(Lys401fs)FrameshiftPVS1 + PS1 + PM2 + PM3 + PP4 (pathogenic)Denora, et al.
Family 2compound heterozygousIntron24c.4162-10 T > GUnknown/unknown/ unknown0Spastic cerebellar ataxic gait, intentional tremor of left hand, cognitive impairmentMissensePM1 + PM2 + PM3 + PP4 (likely pathogenic)Novel
Exon11c.2163dupTUnknown/unknown/ unknown0 p. (Ile722fs)FrameshiftPVS1 + PM2 + PM3 + PP4 (pathogenic)Liao, et al.
Family 3homozygousExon 4c.733_734del 0Walking difficulties, spastic paraparesis, dysarthria, cognitive impairmentp. (Met245fs)FrameshiftPVS1 + PS1 + PM2 + PP4 (pathogenic)Stevanin, et al.
Family 4homozygousExon 22c.3805dupAUnknown/unknown/ unknown0Spastic paraparesis, limb pain, cognitive impairmentp.(Arg1269fs)FrameshiftPVS1 + PM1 + PM2 + PP4 (pathogenic)Novel
Family 5compound heterozygousExon2c.317C > ADeleterious/deleterious/benign0Walking difficulties, spastic paraparesis, tremor in the upper limbs, cognitive impairmentp. (Ala106Asp)MissensePM2 + PP1 + PP3 + PP4 (VUS)Novel
Intron20c.3520 + 3_3520 + 6delUnknown/unknown/ unknown0 Intron deletionPM2 + PP1 + PP4 (VUS)Novel
Family 6homozygousExon 38c.6856C > TUnknown/unknown/ deleterious0.0002Gait abnormality, spastic paraparesis, dysarthria, cognitive impairmentp.(Arg2286X)NonsensePVS1 + PS1 + PM2 + PP4 (pathogenic)Denora. et al.
Family 7homozygousIntron 39c.7151 + 4_7151 + 7delAGTAUnknown/unknown/ unknown0Gait abnormality, spastic paraparesis, cognitive impairmentsplicingPS1 + PS3 + PM2 + PP4 (pathogenic)Liao, et al.
Family 8homozygousIntron 21c.3686 + 3_3686 + 6delGAGTUnknown/unknown/ unknown0Spastic paraparesis, cognitive impairment, walking difficultiesFrameshiftPM2 + PP4 (VUS)Novel
Family 9homozygousExon 7c.1561_1562delAAUnknown/unknown/ unknown0Spastic cerebellar ataxic gait, cognitive impairment, urinary disturbances, dysarthria, dysphagia, distal amyotrophy of lower limbsp.(Asn521Trpfs)FrameshiftPVS1 + PM1 + PM2 + PP4 (pathogenic)Novel
  1. VUS Variants of unknown significance, PVS Very strong evidence of pathogenicity, PS Strong evidence of pathogenicity, PM Moderate evidence of pathogenicity, PP Supporting evidence of pathogenicity; aalso has been identified in a ALS patients