Table 1. Mutations detected in the ATP7B gene in Wilson disease patients during present study.
| Sl.# | Mutation | Exon(E)/ Intron(I) | Type of mutation | Novel/reported | Family (zygosity) | Region of protein | Ethnic origin | Frequency of mutation in affected individuals (%) | Frequency of mutation in other population (%) | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | c.172_173insC (p.Ala58fs*19) |
E2 | Insertion | Novel | Family-B (compound heterozygous with c.3741C>G) & Family-90 (homozygous) | CBD1 | Indian (South) | 1.3 | - | This study |
| 2 | c.220_222delA (p.Lys74fs*9) |
E2 | Deletion | Novel | Family-128 (homozygous) | CBD1 | Indian (South) | 0.8 | - | This study |
| 3 | c.813C>A (p.Cys271*) |
E2 | Nonsense | Reported | Family-N, Family-Q, Family-62, Family-75, Family-D, Family-69, Family-93 & Family-64 (homozygous); Family-A, Family-34 & Family-W (heterozygous) |
CBD3 | German, Turkish, Indian (East), Indian (South), Thai, Indian (West) & Indian (East) | 8.4 | 1.2 (German), 1.9 (Turkish), 16 Indian (East), 10 Indian (South), 2.6 (Thai), 20.2 Indian (West) & 24.2 Indian (East) |
http://www.wilsondisease.med.ualberta.ca/ |
| 4 | c.841C>T (p.Gln281*) |
E2 | Nonsense | Novel | Family-31 (homozygous) | CBD3 | Indian (South) | 0.8 | - | This study |
| 5 | c.1048delC (p.Pro350fs*12) | E2 | Deletion | Novel | Family-60 (homozygous) | Between CBD3 & CBD4 | Indian (South) | 0.8 | - | This study |
| 6 | c.1442C>G (p.Ser481*) |
E3 | Nonsense | Novel | Family-506 (heterozygous) | Between CBD4 & CBD5 | Indian (South) | 0.4 | - | This study |
| 7 | c.1847G>A (p.Arg616Gln) |
E5 | Missense | Reported | Family-67 (heterozygous) | CBD6 | British, Mediterranean, Indian (South) & Chinese–Han | 0.4 | 1 (British), 6 (Mediterranean), 4 Indian (South) & 1 (Chinese-Han) |
http://www.wilsondisease.med.ualberta.ca/ |
| 8 | c.2128G>A (p.Gly710Ser) |
E8 | Missense | Reported | Family-56 (heterozygous) | TMS2 | European, Middle Eastern, Hunagarian & Indian (East) | 0.4 | 1.78 (European), <1 (Middle Eastern), 1.2 (Hunagarian) & 0.8% Indian (East) | http://www.wilsondisease.med.ualberta.ca/ |
| 9 | c.2131G>T (p.Gly711Trp) |
E8 | Missense | Reported | Family-L (compound heterozygous with c.3809A>G); Family-419, Family-S, Family 42, Family-50, Family-53, Family 82 & Family-116 (homozygous); Family-74 (heterozygous) | TMS3 | Pakistani | 7.0 | 1.9 (Pakistani) | http://www.wilsondisease.med.ualberta.ca/ |
| 10 | c.2204T>G (p.Leu735Arg) |
E8 | Missense | Novel | Family-M (homozygous) | TMS3 | Indian (South) | 0.8 | - | This study |
| 11 | c.2255T>G (p.Val752Gly) |
E8 | Missense | Novel | Family-41B (compound heterozygous with c.3182G>A) | TMS3 | Indian (South) | 0.4 | - | This study |
| 12 | c.2267C>T (p.Ala756Val) |
E8 | Missense | Reported | Family-72 (homozygous) | Between TMS3 & TMS4 | Italian | 0.8 | 16.6 (Italian) | http://www.wilsondisease.med.ualberta.ca/ |
| 13 | c.2297C>T (p.Thr766Met) |
E8 | Missense | Reported | Family-72 (homozygous) | TMS4 | British | 0.8 | 0.2 (British) | http://www.wilsondisease.med.ualberta.ca/ |
| 14 | c.2303C>T (p.Pro768Leu) | E8 | Missense | Reported | Family-55 (compound heterozygous with c.3446G>C) | TMS4 | Indian (South) & Spanish | 0.4 | 7.4 Indian (South) & 3.3 Spanish | http://www.wilsondisease.med.ualberta.ca/ |
| 15 | c.2333G>A (p.Arg778Gln) |
E8 | Missense | Reported | Family-P & Family-85 (homozygous) |
TMS4 | Taiwanese, Chinese, Indian (West) & Indian (East) | 1.7 | 4.8 (Taiwanese), 1.5 Chinese,1 Indian (West) & 1 Indian (East) | http://www.wilsondisease.med.ualberta.ca/ |
| 16 | c.2435delA (p.Asn812fs*2) | E9 | Deletion | Novel | Family-77 (heterozygous) | A domain | Indian (South) | 0.4 | - | This study |
| 17 | c.2534T>C (p.Val845Ala) |
E10 | Missense | Novel | Family-80 (homozygous) | A domain | Indian (South) | 0.8 | - | This study |
| 18 | c.2666A>C (p.His889Pro) |
E11 | Missense | Novel | Family-123 (compound heterozygous with c.3155C>T) | A domain | Indian (South) | 0.4 | - | This study |
| 19 | c.2930C>T (p.Thr977Met) |
E13 | Missense | Reported | Family-76 (homozygous) | TMS6 | European, British & Indian (East) | 0.8 | 5.3 European, 2.8 British, 0.5 Indian (East) & 1 Indian (East) | http://www.wilsondisease.med.ualberta.ca/ |
| 20 | c.2998G>A (p.Gly1000Arg) |
E13 | Missense | Reported | Family-46 & Family-118 (homozygous) | Between TMS6 & ATP binding domain | British & Sardinian | 1.7 | 1.6 (British) & 0.4 (Sardinian) | http://www.wilsondisease.med.ualberta.ca/ |
| 21 | c.3008C>T (p.Ala1003Val) | E13 | Missense | Reported | Family-36, Family-54, Family-83 & Family-100 (homozygous) | Between TMS6 & ATP binding domain | Turkish, Indian (South) & Indian (West) | 3.5 | 1 (Turkish), 9.2 Indian (South) & 11 Indian (West) | http://www.wilsondisease.med.ualberta.ca/ |
| 22 | c.3053C>T (p.Ala1018Val) | E13 | Missense | Reported | Family-63 (compound heterozygous with c.3809A>G); Family-121 (Heterozygous) | Between TM6 & ATP binding domain | Czech, Chinese–Han & Sardinian | 0.8 | 0.2 (Czech), 0.7 (Chinese–Han) & 1.3 (Sardinian) | http://www.wilsondisease.med.ualberta.ca/ |
| 23 | c.3155C>T (p.Pro1052Leu) | E14 | Missense | Reported | Family-123 (compound heterozygous with c.2666A>C) | ATP binding domain | British | 0.4 | 0.9 (British) | http://www.wilsondisease.med.ualberta.ca/ |
| 24 | c.3182G>A (p.Gly1061Glu) | E14 | Missense | Reported | Family-O, Family-V, Family-58 & Family-101 (homozygous); Family-38 & Family-78 (heterozygous); Family-41B (compound heterozygous with c.2255T>G) | ATP binding domain | Pakistani, Turkish, Indian (South), Indian (East), Indian (North) & Indian (West) | 4.8 | 1.9 (Pakistani), 3 (Turkish), 3.7 Indian (South), 11 Indian (East), 3.3 Indian (North) & 3 Indian (West) | http://www.wilsondisease.med.ualberta.ca/ |
| 25 | c.3236G>T (p.Cys1079Phe) |
E14 | Missense | Reported | Family-73 (homozygous) | ATP binding domain | Chinese | 0.8 | 0.6 (Chinese) | http://www.wilsondisease.med.ualberta.ca/ |
| 26 | c.3301G>A (p.Gly1101Arg) |
E15 | Missense | Reported | Family-32, Family-43, Family-52, Family-122 & Family-40 (homozygous) | ATP binding domain |
Indian (West) & Indian (East) | 4.4 | 3 Indian (West) & 23 Indian (East) | http://www.wilsondisease.med.ualberta.ca/ |
| 27 | c.3446G>C (p.Gly1149Ala) | E16 | Missense | Reported | Family-T, Family-35 & Family-47 (homozygous); Family-55 (compound heterozygous with c.2303C>T) | ATP binding domain |
Filipino | 3.0 | 0.1 (Filipino) | http://www.wilsondisease.med.ualberta.ca/ |
| 28 | c.3532A>G (p.Thr1178Ala) |
E16 | Missense | Reported | Family-59 & Family-91 (homozygous); Family-E, Family-G & Family-44 (heterozygous) | ATP binding domain |
Taiwanese, Indian (East), Chinese & Indian (East) | 3.0 | 3.4 (Taiwanese), 0.57 Indian (East), 5.5 (Chinese) & 0.5 Indian (East) |
http://www.wilsondisease.med.ualberta.ca/ |
| 29 | c.3551insA (p.Ile1184fs*1) | E16 | Insertion | Novel | Family-86 (homozygous) | ATP binding domain |
Indian (South) | 0.8 | - | This study |
| 30 | c.3722C>T (p.Ala1241Val) |
E18 | Missense | Reported | Family-98 (heterozygous) | ATP binding domain |
Indian (South) & Indian (East) | 0.4 | 1.8 Indian (South) & 5 Indian (East) | http://www.wilsondisease.med.ualberta.ca/ |
| 31 | c.3741C>G (p.His1247Gln) | E18 | Missense | Reported | Family-B (compound heterozygous with c.172_173insC); Family-90 (homozygous) | ATP binding domain |
Indian (East) | 1.3 | 0.2 Indian (East) | http://www.wilsondisease.med.ualberta.ca/ |
| 32 | c.3809A>G (p.Asp1270Ser) | E18 | Missense | Reported | Family-89 (homozygous); Family-L (compound heterozygous with c.2131G>T) & Family-63 (compound heterozygous with c.3053C>T) | ATP binding domain |
Indian (South), Indian (East), Chinese, Indian (North) & Indian (West) | 1.7 | 5.5 Indian (South), 1.7 Indian (East), 0.8 (Chinese), 2.2 Indian (North) & 3 Indian (West) |
http://www.wilsondisease.med.ualberta.ca/ |
| 33 | c.3895C>T (p.Leu1299Phe) |
E18 | Missense | Reported | Family-U & Family-70 (heterozygous) | Between ATP binding domain & TMS7 | Indian (South) & Indian (West) | 0.8 | 1.8 Indian (South) & 3 Indian (West) | http://www.wilsondisease.med.ualberta.ca/ |
| 34 | c.3920T>A (p.Val1307Glu) |
E19 | Missense | Novel | Family-49 (homozygous) | Between ATP binding domain & TMS7 |
Indian (South) | 0.8 | - | This study |
| 35 | c.4015G>C (p.Ala1339Pro) |
E19 | Missense | Novel | Family-C (heterozygous) | TMS7 | Indian (South) | 0.4 | - | This study |
| 36 | c.4021G>A (p.Gly1341Ser) | E19 | Missense | Reported | Family-K (homozygous); Family-Y & Family-57 (heterozygous) | TMS7 | Indian (South) & Indian (West) | 1.7 | 3.7 Indian (South) & 1 Indian (West) | http://www.wilsondisease.med.ualberta.ca/ |