Table 2.

Summary of the mutations identified in CYP4V2 gene in patients with molecular diagnosis of BCD, according to the medical literature.

Number	Exon	CYP4V2 mutation	Protein mutation	Change	Origin	References
1	1	c.31C>T	p.Q11X	Nonsense	Asian (Chinese)68	Meng et al68
2	1	c.64C>G	p.L22V	Missense	European25,55 Asian (Chinese)26,61,68,81	Halford et al25, Li et al26, Jiao et al55, Shan et al61, Meng et al68, Song et al81
3	1	c.65T>A	p.L22H	Missense	Asian (Chinese)56,71,82	Zhang et al56, Yin et al71, Raoof et al82
4	1	c.71T>C	p.L24P	Missense	Unknown55	Jiao et al55
5	1	c.76G>A	p.G26S	Missense	European (Italian)18	Rossi et al18
6	1	c.77G>A	p.G26D	Missense	European25 Asian (Chinese)71	Halford et al25, Yin et al71
7	1	c.130T>A	p.W44R	Missense	European5,55	Li et al5, Jiao et al55
8	1	c.134A>C	p.G45P	Missense	European55	Jiao et al55
9	1	c.181G>A	p.G61S	Missense	Asian (Chinese)5,55	Li et al5, Jiao et al55
10	1	c.197T>G	p.M66R	Missense	South Asian25 unknown55	Halford et al25, Jiao et al55
11	1	c.214+1G>A	Exon1del	Splice site	Asian (Japanese)5	Li et al5
12	1i	c.214+25delT	Exon1del	Splice site	European5	Li et al5
13	2	c.215-2A>G	Exon2del	Splice site	Asian (Chinese)54,68,71	Xiao et al54, Meng et al68, Yin et al71
14	2	c.215-1G>A	Exon2del	Splice site	Asian (Chinese)56,68	Zhang et al56, Meng et al68
15	2	c.219T>A	p.F73L	Missense	Asian (Chinese)33,56,68,69,71	Yin et al33,71, Zhang et al56, Meng et al68, Tian et al69
16	2	c.237G>T	p.E79D	Missense	Asian (Chinese)5,55 Asian (Thailandese)64	Li et al5, Jiao et al55, Jinda et al64
17	2	c.242C>G	p.T81R	Missense	Caucasian58	Astuti et al58
18	2	c.253C>T	p.R85C	Missense	Asian (Chinese)56,61	Zhang et al56, Shan et al61
19	2	c.254G>A	p.R85H	Missense	Asian (Chinese)56	Zhang et al56
20	2	c.277T>C	p.W93R	Missense	European (Italian)18	Rossi et al18
21	2	c.283G>A	p.G95R	Missense	European25 (Spanish)11 Asian (Chinese)33,56,61,68,71 unknown55,79	García-García et al11, Halford et al25, Yin et al33,71, Jiao et al55, Zhang et al56, Shan et al61, Meng et al68, Manzouri et al79
22	2i	c.327+1G>A	p.(Glu72Glyfs*5)	Splice donor variant	Asian (Japanese)5,32,55,57	Li et al5, Miyata et al32,57, Jiao et al55
23	2i	c.327+11G > C	¿?	Splice site	European25	Halford et al25
24	3i	c.328-1G>A	p. (Glu109Tyrfs*30) Exon3del	Splice site	European5,55 Asian (Chinese)56	Li et al5, Jiao et al55, Zhang et al56
25	3	c.332T>C	p.I111T	Missense	European5,55 (Spanish)11 European (Italian)18 lebanese13,58	Li et al5, García-García et al11, Haddad et al13, Rossi et al18, Jiao et al55, Astuti et al58
26	3	c.335T>G	p.L112X	Nonsense	Asian (Chinese)56,61	Zhang et al56, Shan et al61
27	3	362C>A	p.S121Y	Missense	Asian (Japanese)83	Katagiri et al83
28	3	c.364T>C	p.S122P	Missense	European (Italian)18	Rossi et al18
29	3	c.367A>G	p.M123V	Missense	Asian (Chinese)5,55 European55 Asian (Thailandese)64	Li et al5, Jiao et al,55 Jinda et al64
30	3	c.368T>G	p.M123R	Missense	Asian (Chinese)56	Zhang et al56
31	3	c.400G>T	p.G134X	Nonsense	European5,55	Li et al5, Jiao et al55
32	3	c.413+2T>G	Exon3del	Splice site	Asian (Chinese)68	Meng et al68
33	4	c.518T>G	p.L173W	Missense	Asian (Japanese)32,57,76,77 Asian (Chinese)54,71	Miyata et al32,57, Xiao et al54, Yin et al71, Nakamura et al76, Lin et al77
34	5	c.604+4A>G	Exon4del	Splice site	Caucasian58	Astuti et al58
35	5	c.604G>A	p.G202L	Missense	Caucasian58	Astuti et al58
36	5	c.636_640delAAGTA	p.S213X	Nonsense	European25 unknown79	Halford et al25, Manzouri et al79
37	5	c.610G>A	p.A204T	Missense	European (Spanish)11	García-García et al11
38	5	c.655T>C	p.Y219H	Missense	Asian (Chinese)39,50	Lai et al39,50
39	6	c.677T>A	p.M226L	Missense	Middle East25 European55 unknown55	Halford et al25, Jiao et al55
40	6	c.681_4delTGAG	p.S227Rfs*1	Frameshift	Asian (Chinese)71	Yin et al71
41	6	c.694C>T	p.R232X	Nonsense	European55 (Italian)18 Asian (Chinese)55	Rossi et al18, Jiao et al55
42	10	c.710C>A*	¿?	¿?	Asian (Japanese)32,57	Miyata et al32,57
43	6	c.724delG	p.D242Ifs35X	Frameshift	European (Italian)18	Rossi et al18
44	6	c.732delG	p.(Trp244Cysfs*33)	Missense	European (Spanish)11	García-García et al11
45	6	c.732G>A	p.W244X	Nonsense	Asian (Chinese)39,50,56,68	Lai et al39,50, Zhang et al56, Meng et al68
46	6	c.761A>G	p.H254R	Missense	Asian (Chinese)54	Xiao et al54
47	6	c.772C>T	p.L258F	Missense	European (Italian)78	Parravano et al78
48	6	c.775A>C	p.K259Q	Missense	European25,55(Italian)18 Asian (Japanese)70 Asian (Chinese)73,81	Rossi et al18, Halford et al25, Jiao et al55, Gekka et al70, Liu et al73, Song et al81
49	6	c.791delT	Exon6del	Splice site	Asian (Chinese)68	Meng et al68
50	6	c.801+5G>A	Exon6del	Splice site	Asian (Chinese)56	Zhang et al56
51	6i	c.802-8_806del13	Exon7del	Frameshift delection	Asian (Chinese)5 Asian (Japanese)5	Li et al5
52	6i_7	c.802-8_807del	p.(Val268_Glu329del)	Frameshift delection	Asian (Japanese)5 Asian (Chinese)50	Li et al5, Lai et al50
53	7	c.802-9A>G	Altered splicing	Splice site	Asian (Chinese)56	Zhang et al56
54	7	c.802-8_810 del17insGC	Exon7del	Splice site 26	Asian (Japanese)5,21,31,32,45,55,57,61,67,70,72,76,77,86 Asian (Chinese)5,25,26,33,34,39,50,54–56,61,68,69,71,73,75,77,80,82,84 Asian (Korean)55,74,87 European25,58 Unknown55	Li et al5,26, Wada et al21, Halford et al25, Oishi et al31, Miyata et al32,57, Yin et al33,71, Fuerst et al34, Lai et al39,50, Gocho et al45, Xiao et al54, Jiao et al55, Zhang et al56, Astuti et al58, Shan et al61, Yokoi et al67,86, Meng et al68, Tian et al69, Gekka et al70, Jin et al72, Liu et al73, Chung et al74, Lee et al75, Nakamura et al76, Lin et al77, Demile et al80, Raoof et al82, Fu et al84, Park et al87
55	7	c.802-8_810 del17insGT	Exon7del	Splice site 6	Asian (Chinese)71	Yin et al71
56	7	c.810delT	Glu271Asnfs*6	Nonsense	Asian (Chinese)55	Jiao et al55
57	7	c.810T>G	p.Ala27	Synonymous	European25 Asian (Chinese)81	Halford et al25, Song et al81
58	7	c.823G>A	p.Glu275Lys	Missense	European25	Halford et al25
59	7	c.838G>T	p.Glu280*	Nonsense	European55	Jiao et al55
60	7	c.928G>T	p.Glu310*	Nonsense	European55	Jiao et al55
61	7	c.958C>T	p.R320X	Nonsense	Asian (Chinese)54–56,68	Xiao et al54, Jiao et al55, Zhang et al56, Meng et al68
62	7	c.965_7delAAG	p.321delE	Splice site	Asian (Chinese)71	Yin et al71
63	7	c.987+3A>G	¿?	¿?	European25	Halford et al25
64	7	c.971A>T	p.D324V	Missense	Asian (Chinese)39,50	Lai et al39,50
65	7	c.974C>T	p.T325I	Missense	American (Mexican)59	Zenteno et al59
66	8	c.992A>C	p.H331P	Missense	Asian (Chinese)5,26,34,39,50,54–56,61,68,71,77 Asian (Korean)55 unknown55	Li et al5,26, Fuerst et al34, Lai et al39,50, Xiao et al54, Jiao et al55, Zhang et al56, Shan et al61, Meng et al68, Yin et al71, Lin et al77
67	8	C.994G>A	p.D332N	Missense	Asian (Chinese)56,71	Zhang et al56, Yin et al71
68	8	c.998C>A	p.T333K	Missense	European25	Halford et al25
69	8	c.1020G>A	p.W340X	Nonsense	Asian (Japanese)21,70 Asian (Chinese)26,56	Wada et al21, Li et al26, Zhang et al56, Gekka et al70
70	8	c.1021T>C	p.S341P	Missense	European5,55	Li et al5, Jiao et al55
71	8	c.1123delC	p.L375*	¿?	Jew (Yemen)85	Beriozhkin et al85
72	8	c.1027T>G	p.Y343D	Missense	Asian (Chinese)55,68	Jiao et al55, Meng et al68
73	8	c.1062insA	p.V355Sfs*4	Frameshift	Asian (Chinese)33,56,68,71,80 Asian35 (Indian)	Yin et al33,71, Mamatha et al35, Zhang et al56, Meng et al68, Demile et al80
74	8	c.1072G>T	p.E358X	Missense	Asian (Chinese)56	Zhang et al56
75	8i	c.1091-2A>G	p.(Gly364_Val408del) Exon9del	Splice site large delection	Asian (Chinese)5,26,33,39,50,54–56,61,68,69,71,80,81,84	Li et al5,26, Yin et al33,71, Lai et al39,50, Xiao et al54, Jiao et al55, Zhang et al56, Shan et al61, Meng et al68, Tian et al69, Demile et al80, Song et al81, Fu et al84
76	9	c.1157A>C	p.K386T	Missense	Asian (Chinese)75	Lee et al75
77	9	c.1168C>T	p.R390C	Missense	Asian (Chinese)26,56,71 Asian (Japanese)67 unknown55	Li et al26, Jiao et al55, Zhang et al56, Yokoi et al67, Yin et al71
78	9	c.1169G>A	p.R390H	Missense	European (Italian)18 Asian (Chinese)54,56,71 unknown55	Rossi et al18, Xiao et al54, Jiao et al55, Zhang et al56, Yin et al71
79	9	c.1178C>T	p.P393L	Missense	Unknown55	Jiao et al55
80	9	c.1187C>T	p.P396L	Missense	Asian (Chinese)39,50,68 Unknown55	Lai et al39,50, Jiao et al55, Meng et al68
81	9	c.1198C>T	p.R400C	Transversion	Asian (Chinese)39,50,56 European55 (German66) Caucasian58	Lai et al39,50, Jiao et al55, Zhang et al56, Astuti et al58, Lockhart et al66
82	9	c.1199G>A	P.R400H	Missense	Asian (Chinese)39,50,54–56,61,69 Asian (Japanese)32 European25,55	Halford et al25, Miyata et al32, Lai et al39,50, Xiao et al54, Jiao et al55, Zhang et al56, Shan et al61, Tian et al69
83	9	c.1216T>C	p.C406R	Missense	Asian (Chinese)56	Zhang et al56
84	9	c.1219G>T	p.Glu407*	Nonsense	Unknown55	Jiao et al55
85	9i	c.1225+1G>A	p.(Gly364_V408del)	Nonsense skip exon 9	ARABIC55	Jiao et al55
86	10	c.1226-6_1235del16	A409Efs*3	Splice site exon10del	Asian (Chinese)56,61,71 Asian (Japanese)32,57	Miyata et al32,57, Zhang et al56, Shan et al61, Yin et al71
87	10	c.1249dup	p.Thr417Asnfs*2	Frameshift delection	Caucasian58	Astuti et al58
88	10	c.1278G>T	p.L426F	Missense	Asian (Chinese)56	Zhang et al56
89	10	1327C>T	p.R443W	Missense	European (Spanish)11	García-García et al11
90	10	c.1328G>A	p.R443Q	Missense	Asian (Korean)55 European25,55 (Italian)18	Rossi et al18, Halford et al25, Jiao et al55
91	10	c.1348C>T	p.Q450X	Nonsense	Middle East77	Lin et al77
92	10	c.1355G>A	p.R452H	Missense	Asian (Korean)55	Jiao et al55
93	10	c.1372G>A	p.V458M	Missense	Lebanese13 European55	Haddad et al13, Jiao et al55
94	10	c.1378T>C	¿?	¿?	Asian (Japanese)32,57	Miyata et al32,57
95	10	c.1393A>G	p.R465G	Missense	EUROPEAN25,55 (Spanish)11 European (Italian)18 Caucasian58 Unknown55	García-García et al11, Rossi et al18, Halford et al25, Jiao et al55, Astuti et al58
96	10	c.1396A>G	p.N466D	Missense	Asian (Chinese)84	Fu et al84
97	10	c.1399T>C	p.C467R	Missense	Asian (Chinese)81	Song et al81
98	10	c.1400G>A	p.C467Y	Missense	Asian (Chinese)56	Zhang et al56
99	10	c.1437delC	p.T479TfsX7	Frameshift delection	Asian (Chinese)69	Tian et al69
100	11	c.1442delT	p.Ser482Argfs*4	¿?	Asian (Chinese)55	Jiao et al55
101	11	c.1445C>A	p.S482X	Nonsense	Asian (Chinese)75	Lee et al75
102	11	c.1508G>A	p.G503E	Missense	Asian (Chinese)56 Arab (Israel)85	Zhang et al56, Beriozkin et al85
103	11	c.1526C>T	p.P509L	Missense	Asian (Japanese)72	Jin et al72
104	11	c.1573C>A	p.R508H	Missense	European5,55	Li et al5, Jiao et al55

Note: ¿?: Unknown.