Genetic investigation of 211 Chinese families expands the mutational and phenotypical spectra of hereditary retinopathy genes through targeted sequencing technology

Bai, Zhouxian; Xie, Yanchuan; Liu, Lina; Shao, Jingzhi; Liu, Yuying; Kong, Xiangdong

doi:10.1186/s12920-021-00935-w

Table 1 General situation of families with pathogenic or likely pathogenic mutations

From: Genetic investigation of 211 Chinese families expands the mutational and phenotypical spectra of hereditary retinopathy genes through targeted sequencing technology

Fa	Np	Gene	Transcript RefSeq	Ex	NA Changes	AA changes	Hzyo	Pf	Reported	Gm	Disease	SPM	ACMG grade
14	2	RHO	NM_000539	1	c.251 T > C	p.L84P	Het	–	Novel	AD	RP, 4	+ + +	PS4 + PM1 + PM2 + PP1 + PP3
15	4	RHO	NM_000539	2	c.403C > T	p.R135W	Het	0/ 1.082^e−5	Yes[36]	AD	RP, 4	+ + +	PS1 + PM1 + PP1 + PP3
48	1	RHO	NM_000539	3	c.541G > A	p.E181K	Het	–	Yes[37]	AD	RP, 4	+ + +	PS2 + PM2 + PP3
54	2	RHO	NM_000539	2	c.403C > T	p.R135W	Het	0/ 1.082^e−5	Yes[38]	AD	RP, 4	+ + +	PS1 + PM1 + PP1 + PP3
18	3	NDP	NM_000266	2	c.124C > A	p.H42N	Hemi	–	Novel	XL	FEVR2[39]	+ + +	PM2 + PM5 + PP1 + PP3
32	1	NDP	NM_000266	3	c.343C > T	p.R115X	Hemi	–	Yes[40]	XLR	Norrie	+ + +	PVS1 + PS1 + PM2 + PP3
46	1	NDP	NM_000266	3	c.401_402delGA	p.134Wfs13	Hemi	–	Novel	XL	FEVR2	/ / /	PVS1 + PS2 + PM2
55	3	NDP	NM_000266	3	c.268C > T	p.R90C	Hemi	–	Yes[41]	XLR	Norrie	+ + +	PS1 + PM2 + PP1 + PP3
7	1	USH2A	NM_206933	2	c.99_100insT	p.R34Sfs*41	Hom	6.242 ^e−5/ 3.231^e−5	Yes[42]	AR	Usher 2A	/ / /	PVS1 + PS1 + PM2
9	1	USH2A	NM_206933	55	c.10859 T > C	p.I3620T	Het	1.16^e−4/ 1.219^e−5	Yes[43]	AR	Usher 2A/RP, 39	+ + +	PS1 + PM2 + PM3 + PP3
9	1	USH2A	NM_206933	13	c.2802 T > G	p.C934W	Het	2.441^e−3/1.915^e−4	Yes[44]	AR	Usher 2A/RP, 39	+ + +	PS1 + PM2 + PM3 + PP3
47	1	USH2A	NM_206933	63	c.13596dupC	p.S4533Lfs*28	Het	–	Novel	AR	Usher 2A	/ / /	PVS1 + PM2 + PM3
47	1	USH2A	NM_206933	56	c.10962C > A	p.Y3654X	Het	–	Novel	AR	Usher 2A	+ + +	PVS1 + PM2 + PM3 + PP3
27	1	RS1	NM_000330	6	c.598C > T	p.R200C	Hemi	–	Yes[45]	XLR	Retinoschisis	+ + +	PS1 + PM2 + PP3
38	1	RS1	NM_000330	4	c.214G > A	p.E72K	Hemi	0/ 1.678^e−5	Yes[45]	XLR	Retinoschisis	+ + +	PS1 + PM2 + PP3
51	2	RS1	NM_000330	4	c.206_207delTG	p.Leu69Argfs*16	Hemi	–	Yes[46]	XLR	Retinoschisis	/ / /	PVS1 + PS1 + PM2 + PP1
1	1	MERTK	NM_006343	8	c.1186G > T	p.E396X	Het	–	Yes[47]	AR	RP,38	/ / +	PVS1 + PS1 + PM2
1	1	MERTK	NM_006343	3	c.518A > G	p.Y173C	Het	0/ 1.219^e−5	Novel	AR	RP,38	+ + +	PM2 + PM3 + PP3 + PP4
2	2	MERTK	NM_006343	4	c.754delC	p.P252Qfs*3	Hom	–	Novel	AR	RP,38	/ / /	PVS1 + PM2 + PP1

Fa	Np	Gene	Transcript ErfSeq	Ex	NA Changes	AA changes	Hzyo	Pf	Reported	Gm	Disease	SPM	ACMG grade
3	1	CYP4V2	NM_207352	7	c.(802–8)_810delTCATACAGGTCATCGCTinsGC	?p.268_270del/ Splicing	Hom	7.963^e−4/ 6.856^e−5	Yes[48]	AR	Bietti CCD	/ / /	PVS1 + PS1 + PM2
4	2	CYP4V2	NM_207352	7	c.(802–8)_810delTCATACAGGTCATCGCTinsGC	?p.268_270del/ Splicing	Het	7.963^e−4/ 6.856^e−5	Yes[48]	AR	Bietti CCD	/ / /	PVS1 + PS1 + PM2 + PM3 + PP1
4	2	CYP4V2	NM_207352	7	c.958C > T	p.R320X	Het	0/ 4.061^e−6	Yes[49]	AR	Bietti CCD	/ / +	PVS1 + PS1 + PM2 + PM3 + PP1
5	4	FSCN2	NM_001077182	1	c.72delG	p.T25Qfs*120	Het	0.01238/ 8.801^e−4	Yes	AD	RP, 30	/ / /	PVS1 + PS1 + PP1
6	2	FSCN2	NM_001077182	1	c.72delG	p.T25Qfs*120	Het	0.01238/ 8.801^e−4	Yes[50]	AD	RP, 30	/ / /	PVS1 + PS1 + PP1
12	4	PRPF31	NM_015629	11	c.(1074–8)_1079delGTCCCCAGGTACCG	?p.358_360delRYRinsS/ Splicing	Het	–	Novel	AD	RP, 11	/ / /	PVS1 + PM2 + PP1
50	2	PRPF31	NM_015629	12	c.1215delG	p.Val406fs*7	Het	–	Yes[51]	AD	RP, 11	/ / /	PVS1 + PS1 + PM2 + PP1
33	1	RPGR	NM_001034853	15	c.2236_2237delGA	p.E746Rfs*23	Hemi	–	Yes	XLR	MD	/ / /	PVS1 + PS1 + PM2
52	2	RPGR	NM_001034853	15	c.2236_2237delGA	p.E746Rfs*23	Hemi	–	Yes[52]	XLR	MD	/ / /	PVS1 + PS1 + PM2 + PP1
43	5	RP2	NM_006915	3	c.769–2A > G	splicing	Hemi	–	Yes[53]	XL	RP, 2	/ / +	PVS1 + PS1 + PM2 + PP1
44	4	RP2	NM_006915	2	c.572_582dup11	p.Pro190Profs*52	Hemi	–	Novel	XL	RP, 2	/ / /	PVS1 + PM2 + PP1
36	1	ABCA4	NM_000350	29	c.4352 + 1G > A	splicing	Het	0/ 8.123^e−6	Yes[54]	AR	Stargardt 1	/ / +	PVS1 + PS1 + PM2 + PM3
36	1	ABCA4	NM_000350	13	c.1804C > T	p.R602W	Het	2.904^e−4/ 4.477^e−5	Yes[55]	AR	Stargardt 1	+ + +	PS1 + PM2 + PM3 + PP3
11	1	TULP1	NM_003322	13	c.1318C > T	p.R440X	Het	0/ 1.145^e−5	Yes[56]	AR	LCA 15	/ / +	PVS1 + PS1 + PM2
11	1	TULP1	NM_003322	12	c.1142 T > G	p.V381G	Het	–	Novel	AR	LCA 15	+ + +	PM2 + PM3 + PP3 + PP4
16	1	CHM	NM_000390	5	c.544delT	p.C182Vfs*14	Hemi	–	Novel	XLD	choroideremia	/ / /	PVS1 + PM2
28	1	RPGRIP1	NM_020366	16	c.2662C > T	p.R888X	Hom	0/ 1.68^e−5	Yes[57]	AR	LCA6	+ + +	PVS1 + PS1 + PM2 + PP3

Fa	Np	Gene	Transcript RefSeq	Ex	NA Changes	AA changes	Hzyo	Pf	Reported	Gm	Disease	SPM	ACMG grade
17	2	PRPF8	NM_006445	36	c.5792C > T	p.T1931M	Het	–	Novel	AD	RP, 13	+ + +	PM2 + PP1 + PP2 + PP3 + PP4
20	1	TRPM1	NM_0012 52,020	21	c.2789 T > A	p.I930N	Het	–	Novel	AR	CSNB1C	+ + +	PM2 + PM3 + PP2 + PP3
20	1	TRPM1	NM_0012 52,020	22	c.3178 + 1G > A	splicing	Het	6.889^e−4/ 5.772^e−5	Yes[58]	AR	CSNB1C	/ / +	PVS1 + PS1 + PM2
21	1	NR2E3	NM_014249	6	c.925C > T	p.R309W	Hom	0/ 8.34^e−6	Novel	AR	GF	/ + /	PM2 + PM5 + PP2 + PP4
22	1	PAX2	NM_003990	2	c.70dupG	p.V26Gfs*28	Het	0/ 1.237^e−5	Yes[59]	AD	RCS	/ / /	PVS1 + PS1
34	2	KCNV2	NM_133497	1	c.506_513delTGCTGCT	p.V169Gfs*40	Het	–	Novel	AR	RCD3B	/ / /	PVS1 + PM2 + PM3 + PP1
34	2	KCNV2	NM_133497	1	c.137G > A	p.W46X	Het	–	Yes[60]	AR	RCD3B	+ + +	PVS1 + PS1 + PM2 + PP1 + PP3
35	2	FZD4	NM_206933	2	c.612 T > A	p.C204X	Het	–	Novel	AD	FEVR1	+ + +	PVS1 + PM2 + PP1 + PP3
37	2	LRP5	NM_002335	2	c.485_488delACGG	p.H162Rfs*38	Het	–	Novel	AD	FEVR4	/ / /	PVS1 + PM2 + PP1
39	1	SLC38A8	NM_001080442	7	c.927_928delCT	p.Y310Pfs*57	Het	–	Novel	AR	FH2	/ / /	PVS1 + PM2 + PM3
39	1	SLC38A8	NM_001080442	6	c.697G > A	p.E233K	Het	2.778^e−4/ 6.886^e−5	Yes[61]	AR	FH2	+ + +	PS1 + PM2 + PP3
40	1	AIPL1	NM_001285399	3	c.385C > T	p.Q129X	Hom	–	Novel	AR	LCA4	+ + +	PVS1 + PM2 + PP3
41	1	FRMD7	NM_194277	10	c.910C > T	p.R304X	Hemi	0/ 5.608^e−6	Yes[62]	XLR	Nystagmus 1	+ + +	PVS1 + PS1 + PM2 + PP3
42	1	GUCY2D	NM_000180	18	c.3177_3178delAC	p.R1060Rfs*11	Hom	0/ 4.935^e−6	Novel	AR	LCA4	/ / /	PVS1 + PM2
45	1	CNGA1	NM_001142564	5	c.472delC	p.L158Ffs*4	Het	0.0012/ 6.455^e−5	Novel[63]	AR	RP, 49	/ / /	PVS1 + PM2
45	1	CNGA1	NM_001142564	5	c.453C > A	p.Y151X	Het	5.798^e−5/ 4.068^e−6	Novel	AR	RP, 49	+ + +	PVS1 + PM2 + PP3
49	3	TSPAN12	NM_012338	8	c.731delT	p.L244Rfs*17	Het	0/ 4.064^e−6	Novel	AD	EV5	/ / /	PVS1 + PM2 + PP1

Fa denotes Family No.; Np denotes the number of patients; Ex denotes an exon; NA denotes nucleic acid; AA denotes amino acid; Hzyo denotes heterozygosity; Pf denotes the population frequency recorded in the gnomAD database; Gm denotes the genetic model; Disease denotes OMIM disease; SPM denotes SIFT, PolyPhen_2 and Mutation t@sting predicting, ‘ + ’denotes damaging, ‘-’denotes benign, and ‘/’ denotes no data. RP,4 denotes retinitis pigmentosa, type 4; FEVR2 denotes familial exudative vitreoretinopathy, type 2; Usher 2A denotes Usher syndrome, type 2A; RP,39 denotes retinitis pigmentosa, type 39; RP,38 denotes retinitis pigmentosa, type 38; Bietti CCD denotes Bietti crystalline corneoretinal dystrophy; RP, 30 denotes retinitis pigmentosa, type 30; RP, 11 denotes retinitis pigmentosa, type 11; MD denotes macular degeneration, X-linked atrophic; RP,2 denotes retinitis pigmentosa, type 2; Stargardt 1 denotes Stargardt's disease, type1; LCA 15 denotes Leber congenital amaurosis, type 15; LCA6 denotes Leber congenital amaurosis, type 6; RP,13 denotes retinitis pigmentosa, type 13; CSNB1C denotes congenital stationary night blindness, type 1C; GF denotes Goldmann-Favre syndrome; RCS denotes renal coloboma syndrome; RCD3B denotes retinal cone dystrophy, type 3B; FEVR1 denotes familial exudative vitreoretinopathy, type 1; FEVR4 denotes familial exudative vitreoretinopathy, type 4; FH2 denotes foveal hypoplasia, type 2; LCA4 denotes Leber congenital amaurosis, type 4; Nystagmus 1 denotes nystagmus, type 1, congenital, X-linked; RP, 49 denotes retinitis pigmentosa, type 49; EV 5 denotes exudative vitreoretinopathy, type 5

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