Clinical features and genetic spectrum in Chinese patients with recessive hereditary spastic paraplegia

Table 1 Features of variants identified in this study

Gene	dbSNP ID	Exon	Nucleotide change	Amino acid change	Mutation type	Predicted Impact	1000 Genomes	ExAc	GnomAD	Family Segregation	Final Classification^b
SPG11	rs312262720	4	c.733_734delAT^a	p.M245 fs^a	Deletion	NA/NA/NA	absent	0.0001	6.133E-5	yes	Pathogenic
SPG11	rs312262751	16	c.2849dupT^a	p.L950 fs^a	Insertion	NA/NA/NA	absent	absent	4.07e-6	yes	Pathogenic
SPG11	rs749652788	31	c.5934_5935insTAACCTGGAA	p.V1979_L1980delinsX	Insertion	NA/NA/NA	absent	8.26E-6	4.069E-6	yes	Pathogenic
SPG11	NA	39	c.7028_7029delTT	p.F2343 fs	Deletion	NA/NA/NA	absent	absent	absent	yes	Pathogenic
CYP7B1	rs200737038	3	c.334C > T^a	p.R112X^a	Nonsense	NA/NA/A	0.0002	0.0002	0.0001422	yes	Pathogenic
ALDH18A1	NA	7	c.725G > A	p.S242 N	Missense	T/P/D	absent	absent	absent	NA	Pathogenic
GBA2	NA	11	c.1789delG	p.D597fs	Deletion	NA/NA/D	absent	absent	absent	yes	Pathogenic
AP5Z1	rs182694738	2	c.164C > T	p.T55 M	Missense	D/D/D	0.0004	0.0001	0.0001733	NA	Likely Pathogenic
AP5Z1	rs1035120004	7	c.923G > C	p.S308 T	Missense	T/D/D	absent	absent	absent	NA	Likely Pathogenic
CAPN1	NA	6	c.759 + 1G > A^a	–	splicing	NA/NA/D	absent	absent	4.189e-6	yes	Pathogenic
ATP13A2	NA	15	c.1456C > T	p.Q486X	Nonsense	NA/NA/A	absent	absent	absent	yes	Pathogenic

The impact of non-synonymous protein-coding region variants were determined using prediction software including SIFT, PolyPhen-2 and Mutation Taste. SIFT results as Tolerated (T) or Deleterious (D). PolyPhen-2 results as Unknown (UN), Benign (B), Possibly Damaging (P) or Probably Damaging (D). Mutation Taste results as Tolerated (T), Disease causing (D) and Disease causing automatic (A). 1000G, 1000 Genomes Project; ExAC, Exome Aggregation Consortium; ^a, Reported previously; ^b, Variants were finally classified with the functional data according to ACMG guidelines. NA Not available

ISSN: 2047-9158