Current perspectives in Bietti crystalline dystrophy

Figures & data

Figure 1 Infrared images showing a typical pattern of “starry sky” fundus with numerous tiny glittering crystal deposits throughout the entire posterior pole of a patient with BCD (both eyes).

Figure 2 Color retinography of the fundus of both eyes of different patients showing different degrees of evolution of BCD disease, according to Yuzawa classification. (A) Numerous glistening crystalline dots and minimal chorioretinal damage restricted to the posterior pole of the retina, corresponding with stage 1 of Yuzawa. (B) Epithelial confluent atrophy of the posterior pole and few crystalline deposits, corresponding with stage 2 of Yuzawa. (C) Advanced choroidal sclerosis with marked chorioretinal atrophy and absence of deposits, corresponding with stage 2 of Yuzawa. Misdiagnosing with severe forms of choroideremia or retinitis pigmentosa is possible.

Table 1 Presence of corneal crystalline deposits in patients with clinical and genetic diagnosis of BCD confirmed by CYP4V2 gene analysis, according to the medical literature.

Report	Year of publication	Patients with CYP4V2 mutations (number)	Patients with corneal crystalline deposits (number)	Involved CYP4V2 gene mutations (number of patients).	Ethnic origin (number of patients)
Wada et al^Citation21	2005	6	3	c.802-8_810delinsGC/ c.802-8_810delinsGC (3)	JAPANESE (3)
Gekka et al^Citation70	2005	2	0	X	X
Shan et al^Citation61	2005	24	0	X	X
Lin et al^Citation77	2005	11	8	c.802-8_810delinsGC/ c.802-8_810delinsGC (4) c.1348C>T/c.1348C>T (2) c.518T>G/c.518T>G (1) c.802-8_810delinsGC/c.992A>C (1)	CHINESE (5) JAPANESE (2) MIDDLE EAST (2)
Lee et al^Citation75	2005	9	0	X	X
Jin et al^Citation72	2006	3	2	c.802-8_810delinsGC/c.802-8_810delinsGC c.1526C>T/¿?	JAPANESE (2)
Nakamura et al^Citation76	2006	8	5	c.802-8_810delinsGC/ c.802-8_810delinsGC (4) c.802-8_810delinsGC/c.518T>G (1)	JAPANESE (5)
Lai et al^Citation39	2007	14	1	c.802-8_810delinsGC/ c.802-8_810delinsGC	CHINESE
Zenteno et al^Citation59	2008	1	1	c.974C>T/c.974C>T	MEXICAN
Yokoi et al^Citation86	2010	1	1	c.802-8_810delinsGC/ c.802-8_810delinsGC	JAPANESE
Xiao et al^Citation54	2011	21	0	X	X
Mamatha et al^Citation35	2011	3	2	c.1062dupA/¿? ¿?/¿?	INDIAN (2)
Yokoi et al^Citation67	2011	1	1	c.802-8_810delinsGC/c.1168C>T	JAPANESE
Parravano et al^Citation78	2012	1	1	c.772C>T/c.772C>T	ITALIAN
Haddad et al^Citation13	2012	9	0	X	X
Rossi et al^Citation18	2012	15	0	X	X
Song et al^Citation81	2013	3	0	X	X
Chung et al^Citation74	2013	1	1	c.802-8_810delinsGC/ c.802-8_810delinsGC	KOREAN
Yin et al^Citation33	2014	14	0	X	X
Meng et al^Citation68	2014	92	39	¿?	CHINESE (39)
Astuti et al^Citation58	2014	19	3	c.802-8_810delinsGC/c.1198 C>T c.802-8_810delinsGC/¿? p.Thr417Asnfs*2/Genomic delection	CAUCASIAN (3)
Halford et al^Citation25	2014	20	5	c.802-8_810delinsGC/c.1503G>A c.197T>G/c.197T>G c.802-8_810delinsGC/c.802-8_810delinsGC c.677T>A/c.677T>A c.77G>A/c.987+3A>G	ASIAN (4) EUROPEAN (1)
Gocho et al^Citation45	2014	3	0	X	X
Li et al^Citation26	2015	16	1	c.802-8_810delinsGC/c.802-8_810delinsGC	CHINESE
Tian et al^Citation69	2015	5	0	X	X
Park et al^Citation87	2016	1	1	c.802-8_810delinsGC/ c.802-8_810delinsGC	KOREAN
Fuerst et al^Citation34	2016	1	1	c.802-8_810delinsGC/c.992A>C	CHINESE
Raoof et al^Citation82	2016	1	0	X	X
Lockart et al^Citation66	2017	1	1	p.R400C/p.R400C	GERMAN
Zhang et al^Citation56	2018	128	3	c.802-8_810delinsGC/c.802-8_810delinsGC (2)c.802-8_810delinsGC/c.219T>A	CHINESE (3)
García-García et al^Citation11	2018	4	3	p.I111T/p.I111T p.Trp244Cysfs*33/p.G95R p.G95R/p.A204T-pR443W	SPANISH (3)

Note: ¿?: Unknown.

Figure 3 Slit-lamp biomicroscopic findings in several patients with BCD with corneal involvement. Crystalline-like corneal deposits (arrows) can be present in 360º degrees of the limbus area of both eyes.

Figure 4 In vivo confocal microscopy image (400×400 μm) of a BCD patient (subepithelium area). The crystals (yellow arrows) were up to 24 μm in length and 16 μm in width and barely distinguishable from keratocytes nuclei (blue arrows).

Figure 5 Fluorescein angiography in later stage on both eyes of different patients with genetic diagnosis of BCD. (A) Small-patched areas of atrophy of the choriocapillaris and RPE, the macular area remain relatively intact in an early stage of BCD. (B) Marked atrophy of the RPE with focal confluent areas of disappearance of the choriocapillaris. (C) Severe atrophy of the RPE with complete disappearance of the choriocapillaris.

Figure 6 Spectral domain-optical coherence tomography (SD-OCT) image revealing both outer retinal tabulation (blue arrow) and crystalline macular deposits (yellow arrow) of a BCD individual.

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)^Citation68	Meng et al^Citation68
2	1	c.64C>G	p.L22V	Missense	European^Citation25,Citation55 Asian (Chinese)^Citation26,Citation61,Citation68,Citation81	Halford et al^Citation25, Li et al^Citation26, Jiao et al^Citation55, Shan et al^Citation61, Meng et al^Citation68, Song et al^Citation81
3	1	c.65T>A	p.L22H	Missense	Asian (Chinese)^Citation56,Citation71,Citation82	Zhang et al^Citation56, Yin et al^Citation71, Raoof et al^Citation82
4	1	c.71T>C	p.L24P	Missense	Unknown^Citation55	Jiao et al^Citation55
5	1	c.76G>A	p.G26S	Missense	European (Italian)^Citation18	Rossi et al^Citation18
6	1	c.77G>A	p.G26D	Missense	European^Citation25 Asian (Chinese)^Citation71	Halford et al^Citation25, Yin et al^Citation71
7	1	c.130T>A	p.W44R	Missense	European^Citation5,Citation55	Li et al^Citation5, Jiao et al^Citation55
8	1	c.134A>C	p.G45P	Missense	European^Citation55	Jiao et al^Citation55
9	1	c.181G>A	p.G61S	Missense	Asian (Chinese)^Citation5,Citation55	Li et al^Citation5, Jiao et al^Citation55
10	1	c.197T>G	p.M66R	Missense	South Asian^Citation25 unknown^Citation55	Halford et al^Citation25, Jiao et al^Citation55
11	1	c.214+1G>A	Exon1del	Splice site	Asian (Japanese)^Citation5	Li et al^Citation5
12	1i	c.214+25delT	Exon1del	Splice site	European^Citation5	Li et al^Citation5
13	2	c.215-2A>G	Exon2del	Splice site	Asian (Chinese)^Citation54,Citation68,Citation71	Xiao et al^Citation54, Meng et al^Citation68, Yin et al^Citation71
14	2	c.215-1G>A	Exon2del	Splice site	Asian (Chinese)^Citation56,Citation68	Zhang et al^Citation56, Meng et al^Citation68
15	2	c.219T>A	p.F73L	Missense	Asian (Chinese)^Citation33,Citation56,Citation68,Citation69,Citation71	Yin et al^Citation33,Citation71, Zhang et al^Citation56, Meng et al^Citation68, Tian et al^Citation69
16	2	c.237G>T	p.E79D	Missense	Asian (Chinese)^Citation5,Citation55 Asian (Thailandese)^Citation64	Li et al^Citation5, Jiao et al^Citation55, Jinda et al^Citation64
17	2	c.242C>G	p.T81R	Missense	Caucasian^Citation58	Astuti et al^Citation58
18	2	c.253C>T	p.R85C	Missense	Asian (Chinese)^Citation56,Citation61	Zhang et al^Citation56, Shan et al^Citation61
19	2	c.254G>A	p.R85H	Missense	Asian (Chinese)^Citation56	Zhang et al^Citation56
20	2	c.277T>C	p.W93R	Missense	European (Italian)^Citation18	Rossi et al^Citation18
21	2	c.283G>A	p.G95R	Missense	European^Citation25 (Spanish)^Citation11 Asian (Chinese)^Citation33,Citation56,Citation61,Citation68,Citation71 unknown^Citation55,Citation79	García-García et al^Citation11, Halford et al^Citation25, Yin et al^Citation33,Citation71, Jiao et al^Citation55, Zhang et al^Citation56, Shan et al^Citation61, Meng et al^Citation68, Manzouri et al^Citation79
22	2i	c.327+1G>A	p.(Glu72Glyfs*5)	Splice donor variant	Asian (Japanese)^Citation5,Citation32,Citation55,Citation57	Li et al^Citation5, Miyata et al^Citation32,Citation57, Jiao et al^Citation55
23	2i	c.327+11G > C	¿?	Splice site	European^Citation25	Halford et al^Citation25
24	3i	c.328-1G>A	p. (Glu109Tyrfs*30) Exon3del	Splice site	European^Citation5,Citation55 Asian (Chinese)^Citation56	Li et al^Citation5, Jiao et al^Citation55, Zhang et al^Citation56
25	3	c.332T>C	p.I111T	Missense	European^Citation5,Citation55 (Spanish)^Citation11 European (Italian)^Citation18 lebanese^Citation13,Citation58	Li et al^Citation5, García-García et al^Citation11, Haddad et al^Citation13, Rossi et al^Citation18, Jiao et al^Citation55, Astuti et al^Citation58
26	3	c.335T>G	p.L112X	Nonsense	Asian (Chinese)^Citation56,Citation61	Zhang et al^Citation56, Shan et al^Citation61
27	3	362C>A	p.S121Y	Missense	Asian (Japanese)^Citation83	Katagiri et al^Citation83
28	3	c.364T>C	p.S122P	Missense	European (Italian)^Citation18	Rossi et al^Citation18
29	3	c.367A>G	p.M123V	Missense	Asian (Chinese)^Citation5,Citation55 European^Citation55 Asian (Thailandese)^Citation64	Li et al^Citation5, Jiao et al,^Citation55 Jinda et al^Citation64
30	3	c.368T>G	p.M123R	Missense	Asian (Chinese)^Citation56	Zhang et al^Citation56
31	3	c.400G>T	p.G134X	Nonsense	European^Citation5,Citation55	Li et al^Citation5, Jiao et al^Citation55
32	3	c.413+2T>G	Exon3del	Splice site	Asian (Chinese)^Citation68	Meng et al^Citation68
33	4	c.518T>G	p.L173W	Missense	Asian (Japanese)^Citation32,Citation57,Citation76,Citation77 Asian (Chinese)^Citation54,Citation71	Miyata et al^Citation32,Citation57, Xiao et al^Citation54, Yin et al^Citation71, Nakamura et al^Citation76, Lin et al^Citation77
34	5	c.604+4A>G	Exon4del	Splice site	Caucasian^Citation58	Astuti et al^Citation58
35	5	c.604G>A	p.G202L	Missense	Caucasian^Citation58	Astuti et al^Citation58
36	5	c.636_640delAAGTA	p.S213X	Nonsense	European^Citation25 unknown^Citation79	Halford et al^Citation25, Manzouri et al^Citation79
37	5	c.610G>A	p.A204T	Missense	European (Spanish)^Citation11	García-García et al^Citation11
38	5	c.655T>C	p.Y219H	Missense	Asian (Chinese)^Citation39,Citation50	Lai et al^Citation39,Citation50
39	6	c.677T>A	p.M226L	Missense	Middle East^Citation25 European^Citation55 unknown^Citation55	Halford et al^Citation25, Jiao et al^Citation55
40	6	c.681_4delTGAG	p.S227Rfs*1	Frameshift	Asian (Chinese)^Citation71	Yin et al^Citation71
41	6	c.694C>T	p.R232X	Nonsense	European^Citation55 (Italian)^Citation18 Asian (Chinese)^Citation55	Rossi et al^Citation18, Jiao et al^Citation55
42	10	c.710C>A*	¿?	¿?	Asian (Japanese)^Citation32,Citation57	Miyata et al^Citation32,Citation57
43	6	c.724delG	p.D242Ifs35X	Frameshift	European (Italian)^Citation18	Rossi et al^Citation18
44	6	c.732delG	p.(Trp244Cysfs*33)	Missense	European (Spanish)^Citation11	García-García et al^Citation11
45	6	c.732G>A	p.W244X	Nonsense	Asian (Chinese)^Citation39,Citation50,Citation56,Citation68	Lai et al^Citation39,Citation50, Zhang et al^Citation56, Meng et al^Citation68
46	6	c.761A>G	p.H254R	Missense	Asian (Chinese)^Citation54	Xiao et al^Citation54
47	6	c.772C>T	p.L258F	Missense	European (Italian)^Citation78	Parravano et al^Citation78
48	6	c.775A>C	p.K259Q	Missense	European^Citation25,Citation55(Italian)^Citation18 Asian (Japanese)^Citation70 Asian (Chinese)^Citation73,Citation81	Rossi et al^Citation18, Halford et al^Citation25, Jiao et al^Citation55, Gekka et al^Citation70, Liu et al^Citation73, Song et al^Citation81
49	6	c.791delT	Exon6del	Splice site	Asian (Chinese)^Citation68	Meng et al^Citation68
50	6	c.801+5G>A	Exon6del	Splice site	Asian (Chinese)^Citation56	Zhang et al^Citation56
51	6i	c.802-8_806del13	Exon7del	Frameshift delection	Asian (Chinese)^Citation5 Asian (Japanese)^Citation5	Li et al^Citation5
52	6i_7	c.802-8_807del	p.(Val268_Glu329del)	Frameshift delection	Asian (Japanese)^Citation5 Asian (Chinese)^Citation50	Li et al^Citation5, Lai et al^Citation50
53	7	c.802-9A>G	Altered splicing	Splice site	Asian (Chinese)^Citation56	Zhang et al^Citation56
54	7	c.802-8_810 del17insGC	Exon7del	Splice site 26	Asian (Japanese)^Citation5,Citation21,Citation31,Citation32,Citation45,Citation55,Citation57,Citation61,Citation67,Citation70,Citation72,Citation76,Citation77,Citation86 Asian (Chinese)^Citation5,Citation25,Citation26,Citation33,Citation34,Citation39,Citation50,Citation54^–^Citation56,Citation61,Citation68,Citation69,Citation71,Citation73,Citation75,Citation77,Citation80,Citation82,Citation84 Asian (Korean)^Citation55,Citation74,Citation87 European^Citation25,Citation58 Unknown^Citation55	Li et al^Citation5,Citation26, Wada et al^Citation21, Halford et al^Citation25, Oishi et al^Citation31, Miyata et al^Citation32,Citation57, Yin et al^Citation33,Citation71, Fuerst et al^Citation34, Lai et al^Citation39,Citation50, Gocho et al^Citation45, Xiao et al^Citation54, Jiao et al^Citation55, Zhang et al^Citation56, Astuti et al^Citation58, Shan et al^Citation61, Yokoi et al^Citation67,Citation86, Meng et al^Citation68, Tian et al^Citation69, Gekka et al^Citation70, Jin et al^Citation72, Liu et al^Citation73, Chung et al^Citation74, Lee et al^Citation75, Nakamura et al^Citation76, Lin et al^Citation77, Demile et al^Citation80, Raoof et al^Citation82, Fu et al^Citation84, Park et al^Citation87
55	7	c.802-8_810 del17insGT	Exon7del	Splice site 6	Asian (Chinese)^Citation71	Yin et al^Citation71
56	7	c.810delT	Glu271Asnfs*6	Nonsense	Asian (Chinese)^Citation55	Jiao et al^Citation55
57	7	c.810T>G	p.Ala27	Synonymous	European^Citation25 Asian (Chinese)^Citation81	Halford et al^Citation25, Song et al^Citation81
58	7	c.823G>A	p.Glu275Lys	Missense	European^Citation25	Halford et al^Citation25
59	7	c.838G>T	p.Glu280*	Nonsense	European^Citation55	Jiao et al^Citation55
60	7	c.928G>T	p.Glu310*	Nonsense	European^Citation55	Jiao et al^Citation55
61	7	c.958C>T	p.R320X	Nonsense	Asian (Chinese)^Citation54^–^Citation56,Citation68	Xiao et al^Citation54, Jiao et al^Citation55, Zhang et al^Citation56, Meng et al^Citation68
62	7	c.965_7delAAG	p.321delE	Splice site	Asian (Chinese)^Citation71	Yin et al^Citation71
63	7	c.987+3A>G	¿?	¿?	European^Citation25	Halford et al^Citation25
64	7	c.971A>T	p.D324V	Missense	Asian (Chinese)^Citation39,Citation50	Lai et al^Citation39,Citation50
65	7	c.974C>T	p.T325I	Missense	American (Mexican)^Citation59	Zenteno et al^Citation59
66	8	c.992A>C	p.H331P	Missense	Asian (Chinese)^Citation5,Citation26,Citation34,Citation39,Citation50,Citation54^–^Citation56,Citation61,Citation68,Citation71,Citation77 Asian (Korean)^Citation55 unknown^Citation55	Li et al^Citation5,Citation26, Fuerst et al^Citation34, Lai et al^Citation39,Citation50, Xiao et al^Citation54, Jiao et al^Citation55, Zhang et al^Citation56, Shan et al^Citation61, Meng et al^Citation68, Yin et al^Citation71, Lin et al^Citation77
67	8	C.994G>A	p.D332N	Missense	Asian (Chinese)^Citation56,Citation71	Zhang et al^Citation56, Yin et al^Citation71
68	8	c.998C>A	p.T333K	Missense	European^Citation25	Halford et al^Citation25
69	8	c.1020G>A	p.W340X	Nonsense	Asian (Japanese)^Citation21,Citation70 Asian (Chinese)^Citation26,Citation56	Wada et al^Citation21, Li et al^Citation26, Zhang et al^Citation56, Gekka et al^Citation70
70	8	c.1021T>C	p.S341P	Missense	European^Citation5,Citation55	Li et al^Citation5, Jiao et al^Citation55
71	8	c.1123delC	p.L375*	¿?	Jew (Yemen)^Citation85	Beriozhkin et al^Citation85
72	8	c.1027T>G	p.Y343D	Missense	Asian (Chinese)^Citation55,Citation68	Jiao et al^Citation55, Meng et al^Citation68
73	8	c.1062insA	p.V355Sfs*4	Frameshift	Asian (Chinese)^Citation33,Citation56,Citation68,Citation71,Citation80 Asian^Citation35 (Indian)	Yin et al^Citation33,Citation71, Mamatha et al^Citation35, Zhang et al^Citation56, Meng et al^Citation68, Demile et al^Citation80
74	8	c.1072G>T	p.E358X	Missense	Asian (Chinese)^Citation56	Zhang et al^Citation56
75	8i	c.1091-2A>G	p.(Gly364_Val408del) Exon9del	Splice site large delection	Asian (Chinese)^Citation5,Citation26,Citation33,Citation39,Citation50,Citation54^–^Citation56,Citation61,Citation68,Citation69,Citation71,Citation80,Citation81,Citation84	Li et al^Citation5,Citation26, Yin et al^Citation33,Citation71, Lai et al^Citation39,Citation50, Xiao et al^Citation54, Jiao et al^Citation55, Zhang et al^Citation56, Shan et al^Citation61, Meng et al^Citation68, Tian et al^Citation69, Demile et al^Citation80, Song et al^Citation81, Fu et al^Citation84
76	9	c.1157A>C	p.K386T	Missense	Asian (Chinese)^Citation75	Lee et al^Citation75
77	9	c.1168C>T	p.R390C	Missense	Asian (Chinese)^Citation26,Citation56,Citation71 Asian (Japanese)^Citation67 unknown^Citation55	Li et al^Citation26, Jiao et al^Citation55, Zhang et al^Citation56, Yokoi et al^Citation67, Yin et al^Citation71
78	9	c.1169G>A	p.R390H	Missense	European (Italian)^Citation18 Asian (Chinese)^Citation54,Citation56,Citation71 unknown^Citation55	Rossi et al^Citation18, Xiao et al^Citation54, Jiao et al^Citation55, Zhang et al^Citation56, Yin et al^Citation71
79	9	c.1178C>T	p.P393L	Missense	Unknown^Citation55	Jiao et al^Citation55
80	9	c.1187C>T	p.P396L	Missense	Asian (Chinese)^Citation39,Citation50,Citation68 Unknown^Citation55	Lai et al^Citation39,Citation50, Jiao et al^Citation55, Meng et al^Citation68
81	9	c.1198C>T	p.R400C	Transversion	Asian (Chinese)^Citation39,Citation50,Citation56 European^Citation55 (German^Citation66) Caucasian^Citation58	Lai et al^Citation39,Citation50, Jiao et al^Citation55, Zhang et al^Citation56, Astuti et al^Citation58, Lockhart et al^Citation66
82	9	c.1199G>A	P.R400H	Missense	Asian (Chinese)^Citation39,Citation50,Citation54^–^Citation56,Citation61,Citation69 Asian (Japanese)^Citation32 European^Citation25,Citation55	Halford et al^Citation25, Miyata et al^Citation32, Lai et al^Citation39,Citation50, Xiao et al^Citation54, Jiao et al^Citation55, Zhang et al^Citation56, Shan et al^Citation61, Tian et al^Citation69
83	9	c.1216T>C	p.C406R	Missense	Asian (Chinese)^Citation56	Zhang et al^Citation56
84	9	c.1219G>T	p.Glu407*	Nonsense	Unknown^Citation55	Jiao et al^Citation55
85	9i	c.1225+1G>A	p.(Gly364_V408del)	Nonsense skip exon 9	ARABIC^Citation55	Jiao et al^Citation55
86	10	c.1226-6_1235del16	A409Efs*3	Splice site exon10del	Asian (Chinese)^Citation56,Citation61,Citation71 Asian (Japanese)^Citation32,Citation57	Miyata et al^Citation32,Citation57, Zhang et al^Citation56, Shan et al^Citation61, Yin et al^Citation71
87	10	c.1249dup	p.Thr417Asnfs*2	Frameshift delection	Caucasian^Citation58	Astuti et al^Citation58
88	10	c.1278G>T	p.L426F	Missense	Asian (Chinese)^Citation56	Zhang et al^Citation56
89	10	1327C>T	p.R443W	Missense	European (Spanish)^Citation11	García-García et al^Citation11
90	10	c.1328G>A	p.R443Q	Missense	Asian (Korean)^Citation55 European^Citation25,Citation55 (Italian)^Citation18	Rossi et al^Citation18, Halford et al^Citation25, Jiao et al^Citation55
91	10	c.1348C>T	p.Q450X	Nonsense	Middle East^Citation77	Lin et al^Citation77
92	10	c.1355G>A	p.R452H	Missense	Asian (Korean)^Citation55	Jiao et al^Citation55
93	10	c.1372G>A	p.V458M	Missense	Lebanese^Citation13 European^Citation55	Haddad et al^Citation13, Jiao et al^Citation55
94	10	c.1378T>C	¿?	¿?	Asian (Japanese)^Citation32,Citation57	Miyata et al^Citation32,Citation57
95	10	c.1393A>G	p.R465G	Missense	EUROPEAN^Citation25,Citation55 (Spanish)^Citation11 European (Italian)^Citation18 Caucasian^Citation58 Unknown^Citation55	García-García et al^Citation11, Rossi et al^Citation18, Halford et al^Citation25, Jiao et al^Citation55, Astuti et al^Citation58
96	10	c.1396A>G	p.N466D	Missense	Asian (Chinese)^Citation84	Fu et al^Citation84
97	10	c.1399T>C	p.C467R	Missense	Asian (Chinese)^Citation81	Song et al^Citation81
98	10	c.1400G>A	p.C467Y	Missense	Asian (Chinese)^Citation56	Zhang et al^Citation56
99	10	c.1437delC	p.T479TfsX7	Frameshift delection	Asian (Chinese)^Citation69	Tian et al^Citation69
100	11	c.1442delT	p.Ser482Argfs*4	¿?	Asian (Chinese)^Citation55	Jiao et al^Citation55
101	11	c.1445C>A	p.S482X	Nonsense	Asian (Chinese)^Citation75	Lee et al^Citation75
102	11	c.1508G>A	p.G503E	Missense	Asian (Chinese)^Citation56 Arab (Israel)^Citation85	Zhang et al^Citation56, Beriozkin et al^Citation85
103	11	c.1526C>T	p.P509L	Missense	Asian (Japanese)^Citation72	Jin et al^Citation72
104	11	c.1573C>A	p.R508H	Missense	European^Citation5,Citation55	Li et al^Citation5, Jiao et al^Citation55

Note: ¿?: Unknown.

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