Table 4 Mutation spectrum in the IDS gene in patients with MPS II
Family number | Patient number | Age at diagnosis | Enzyme activity in plasma (N = 297–705 nmol/4h/ml) | Enzyme activity in dried blood spots (N = 2.5–50 μmM/l/h) | Phenotype | Nucleotide/protein change in IDS gene |
|---|---|---|---|---|---|---|
1 | 1 | 7 | 16.2 | Mild | c.187A>G; p.Aspn63Asp | |
2 | 2 | 31 | 21.1 | Mild | c.187A>G; p.Aspn63Asp | |
3 | 32 | 18.2 | Mild | c.187A>G; p.Aspn63Asp | ||
3 | 4 | 8 | 1.2 | Mild | c.236C>A; p.Ala79Glu | |
5 | 10 | 8.4 | Mild | c.236C>A; p.Ala79Glu | ||
4 | 6 | 11 | 7.4 | Mild | c.305T>G; p.Leu102Arg | |
7 | 9 | 8.1 | Mild | c.305T>G; p.Leu102Arg | ||
5 | 8 | 55 | – | 0.01 | Mild | c.590C>T; p.Pro197Leu |
9 | 12 | – | 0.01 | Mild | c.590C>T; p.Pro197Leu | |
10 | 5 | – | 0.01 | Mild | c.590C>T; p.Pro197Leu | |
11 | 11 | – | 0.01 | Mild | c.590C>T; p.Pro197Leu | |
6 | 12 | 16 | 14.7 | Mild | c.593A>G; p.Asp198Gly | |
7 | 13 | 23 | 8.4 | Mild | c.1019G>A; p.Gly340Asp | |
14 | 19 | 6.1 | Mild | c.1019G>A; p.Gly340Asp | ||
8 | 15 | 33 | 11.7 | Mild | c.1019G>A; p.Gly340Asp | |
9 | 16 | 35 | 0.01 | Mild | p.1037C>T; p.Ala346Val | |
17 | 23 | 0.05 | Mild | p.1037C>T; p.Ala346Val | ||
18 | 18 | 0.07 | Mild | p.1037C>T; p.Ala346Val | ||
10 | 19 | 15 | 3.6 | Mild | c.1234G>T; p.Gly412Term | |
11 | 20 | 11 | 9.4 | Mild -> intermediate | c.253G>A; p.Ala85Thr | |
12 | 21 | 9 | 10.4 | Mild -> intermediate | c.253G>A; p.Ala85Thr | |
13 | 22 | 6 | 18.6 | Mild -> intermediate | c.253G>A; p.Ala85Thr | |
14 | 23 | 9 | 14.4 | Mild -> intermediate | c.253G>A; p.Ala85Thr | |
15 | 24 | 13 | 0.01 | Mild -> intermediate | c.253G>A; p.Ala85Thr | |
16 | 25 | 8 | 0.02 | Mild -> intermediate | c.253G>T; p.Ala85Ser | |
17 | 26 | 13 | 11.3 | Mild -> intermediate | c.587T>C; p.Leu196Ser | |
18 | 27 | 5 | 4.7 | Mild -> intermediate | c.587T>C; p.Leu196Ser | |
19 | 28 | 2 | 2.1 | Mild -> intermediate | c.1204G>A; p.Glu402Lys | |
20 | 29 | 3 | 1.4 | Mild -> intermediate | c.1204G>A; p.Glu402Lys | |
21 | 30 | 4 | – | 0.01 | Mild -> intermediate | c.1438_1442delCCGAG; p.Pro480Phefs |
22 | 31 | 28 | 14.8 | Mild -> intermediate | c.1028G>A; p.Gly343Glu | |
23 | 32 | 11 | 7.4 | Mild -> intermediate | c.1034G>C; p.Trp345Ser | |
24 | 33 | 25 | 4.8 | Mild -> intermediate | c.1035G>C, p.Trp345Cys | |
25 | 34 | 8 | 5.1 | Mild -> intermediate | IVS2 as C-G -9; c.241-9C>G | |
35 | 10 | 5.2 | Mild -> intermediate | IVS2 as C-G -9; c.241-9C>G | ||
26 | 36 | 7 | 0.1 | Intermediate -> severe | c.283A>T; p.Arg95Trp | |
27 | 37 | 7 | 0.01 | Intermediate -> severe | c.512G>A; p.Cys171Tyr | |
28 | 38 | 5 | 8.4 | Intermediate -> severe | c.545T>C; p.Leu182Pro | |
29 | 39 | 6 | 2.3 | Intermediate -> severe | c.551G>T; p.Cys184Phe | |
30 | 40 | 6 | 2.7 | Intermediate -> severe | c.1327C>T; p.Arg443Term | |
31 | 41 | 7 | 3.18 | Intermediate -> severe | c.1327C>T; p.Arg443Term | |
32 | 42 | 2 | – | 0.01 | Intermediate -> severe | c.1327C>T; p.Arg443Term |
33 | 43 | 13 | 21.6 | Intermediate -> severe | c.1411G>C; p.Asp471His c.1418C>T; p.Pro473Leu | |
34 | 44 | 14 | 2.2 | Intermediate -> severe | IVS6 ds G-A +1; c.879+1G>A | |
35 | 45 | 11 | 0.01 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
36 | 46 | 11 | 0.01 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
37 | 47 | 6 | 0.02 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
38 | 48 | 8 | 0.01 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
39 | 49 | 4 | 0.01 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
40 | 50 | 5 | 2.2 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
41 | 51 | 3 | 0.01 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
42 | 52 | 7 | 0.01 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
43 | 53 | 18 | 0.01 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
44 | 54 | 4 | 4.9 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
45 | 55 | 7 | 2.3 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
46 | 56 | 4 | 7.2 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | |
47 | 57 | 5 | Intermediate -> severe | IVS8 ds C-T -59; c.1122C>T | ||
48 | 58 | 3 | 4.9 | Intermediate -> severe | c.118_120delCTC; p.Leu40del | |
49 | 59 | 4 | 21.4 | Intermediate -> severe | c.121_123delCTC p.Leu41del | |
50 | 60 | 6 | 0.01 | Intermediate -> severe | c.625_627del TTG p.Leu209del | |
51 | 61 | 9 | 4.4 | Intermediate -> severe | c.1426_1437 del12; p.476_479delAsnSerAspLys | |
52 | 62 | 6 | 8.3 | Severe | c.103G>C; p.Asp35His | |
63 | 4 | 10.4 | Severe | c.103G>C; p.Asp35His | ||
53 | 64 | 3 | 0.35 | Severe | c.136G>T; p.Asp46Tyr | |
54 | 65 | 3 | – | 0.01 | Severe | c.136G>A; p.Asp46Asn |
55 | 66 | 4 | 0.1 | Severe | c.160T>G; p.Tyr54Asp | |
56 | 67 | 4 | 4.6 | Severe | c.257C>T; p. Pro86Leu | |
57 | 68 | 5 | 5.1 | Severe | c.257C>T; p. Pro86Leu | |
58 | 69 | 2 | 3.5 | Severe | c.257C>T; p. Pro86Leu | |
59 | 70 | 10 | 11.8 | Severe | c.257C>G; p. Pro86Arg | |
60 | 71 | 6 | 0.01 | Severe | c.263G>A; p.Arg88His | |
72 | 3 | 0.01 | Severe | c.263G>A; p.Arg88His | ||
61 | 73 | 3 | 0.7 | Severe | c.263G>A; p.Arg88His | |
74 | 4 | 0.8 | Severe | c.263G>A; p.Arg88His | ||
62 | 75 | 7 | – | 0.01 | Severe | c.263G>A; p.Arg88His |
63 | 76 | 3 | 0.01 | Severe | c.263G>A; p.Arg88His | |
64 | 77 | 5 | 0.01 | Severe | c.263G>T; p.Arg88Leu | |
65 | 78 | 4 | 0.02 | Severe | c.262C>T; p.Arg88Cys | |
66 | 79 | 5 | 0.01 | Severe | c.262C>T; p.Arg88Cys | |
67 | 80 | 4 | 0.01 | Severe | c.262C>T; p.Arg88Cys | |
68 | 81 | 3 | 0.01 | Severe | c.262C>T; p.Arg88Cys | |
69 | 82 | 4 | 3.2 | Severe | c.263G>C; p.Arg88Pro | |
70 | 83 | 8 | 0.01 | Severe | c.307T>G; p.Tyr103Asp | |
71 | 84 | 5 | 4.8 | Severe | c.325T>C; p.Trp109Arg | |
72 | 85 | 6 | 1.37 | Severe | c.325T>C; p.Trp109Arg | |
73 | 86 | 1 | – | 0.01 | Severe | c.359C>G; p.Pro120Arg |
74 | 87 | 4 | 0.01 | Severe | c.395C>G; p.Ser132Trp | |
75 | 88 | 9 | 0.01 | Severe | c.395C>G; p.Ser132Trp | |
76 | 89 | 3 | 0.01 | Severe | c.403A>G; p.Lys135Glu | |
77 | 90 | 10 | 0.1 | Severe | c.476A>C; p.His159Pro | |
78 | 91 | 5 | 0.01 | Severe | c.671G>A; p.Gly224Glu | |
79 | 92 | 5 | 1.2 | Severe | c.697A>G; p.Arg233Gly | |
93 | 2 | 1.59 | Severe | c.697A>G; p.Arg233Gly | ||
80 | 94 | 1.5 | 0.01 | Severe | c.697A>G; p.Arg233Gly | |
81 | 95 | 15 | 4.1 | Severe | c.776T>C; p.Leu259Pro | |
82 | 96 | 3 | 0.15 | Severe | c.795C>A; p.Asn265Lys | |
83 | 97 | 3 | 0.49 | Severe | c.795C>A; p.Asn265Lys | |
84 | 98 | 3 | 10.8 | Severe | c.795C>G; p.Asn265Lys | |
85 | 99 | 10 | 0.01 | Severe | c.998C>T; p.Ser333Leu | |
86 | 100 | 7 | 0.01 | Severe | c.998C>T; p.Ser333Leu | |
87 | 101 | 6 | 0.01 | Severe | c.998C>T; p.Ser333Leu | |
88 | 102 | 7 | 0.01 | Severe | c.998C>T; p.Ser333Leu | |
89 | 103 | 5 | 0.01 | Severe | c.998C>T; p.Ser333Leu | |
90 | 104 | 7 | 0.01 | Severe | c.998C>T; p.Ser333Leu | |
91 | 105 | 1 | 3.5 | Severe | c.998C>T; p.Ser333Leu | |
92 | 106 | 2 | 0.01 | Severe | c.1004A>G; p.His335Arg | |
93 | 107 | 5 | 2.7 | Severe | c.1006G>C; p.Gly336Arg | |
94 | 108 | 10 | 0.1 | Severe | c.1295G>A; p.Cys432Tyr | |
95 | 109 | 4 | 0.01 | Severe | c.1295G>A; p.Cys432Tyr | |
96 | 110 | 4 | 5.4 | Severe | c.1402C>T; p.Arg468Trp | |
97 | 111 | 2 | 0.1 | Severe | c.1402C>T; p.Arg468Trp | |
98 | 112 | 3 | 0.01 | Severe | c.1402C>T; p.Arg468Trp | |
99 | 113 | 5 | 0.1 | Severe | c.1402C>T; p.Arg468Trp | |
100 | 114 | 3 | – | 0.01 | Severe | c.1402C>T; p.Arg468Trp |
101 | 115 | 3 | 0.01 | Severe | c.1403G>A; p.Arg468Gln | |
102 | 116 | 3 | 0.9 | Severe | c.1403G>A; p.Arg468Gln | |
117 | 3 | 0.01 | Severe | c.1403G>A; p.Arg468Gln | ||
103 | 118 | 5 | 1.4 | Severe | c.1403G>A; p.Arg468Gln | |
104 | 119 | 2 | 0.01 | Severe | c.1403G>A; p.Arg468Gln | |
105 | 120 | 2 | 6.3 | Severe | c.1403G>A; p.Arg468Gln | |
121 | 4 | 2.8 | Severe | c.1403G>A; p.Arg468Gln | ||
106 | 122 | 3 | 10.8 | Severe | c.1403G>A; p.Arg468Gln | |
107 | 123 | 4 | 0.01 | Severe | c.1403G>A; p.Arg468Gln | |
108 | 124 | 2 | 3.12 | Severe | c.1403G>A; p.Arg468Gln | |
109 | 125 | 4 | 0.01 | Severe | c.1432G>T; p.Asp478Tyr | |
110 | 126 | 7 | 0.1 | Severe | c.1432G>A; p.Asp478Asn | |
111 | 127 | 6 | 0.01 | Severe | c.1454T>G; p.Ileu485Arg | |
112 | 128 | 6 | 0.01 | Severe | c.1454T>G; p.Ileu485Arg | |
113 | 129 | 8 | 0.01 | Severe | c.1565T>C; p.Leu522Pro | |
114 | 130 | 3 | 0.15 | Severe | c.196C>T; p.Gln66Term | |
115 | 131 | 2 | 0.01 | Severe | c.361C>T; p.Gln121Term | |
116 | 132 | 3 | 4.5 | Severe | c.514C>T; p.Arg172Term | |
117 | 133 | 4 | 2.7 | Severe | c.514C>T; p.Arg172Term | |
118 | 134 | 2 | 7.8 | Severe | c.514C>T; p.Arg172Term | |
119 | 135 | 4 | 4.32 | Severe | c.514C>T; p.Arg172Term | |
120 | 136 | 4 | 8.4 | Severe | c.514C>T; p.Arg172Term | |
121 | 137 | 2 | – | 0.01 | Severe | c.514C>T; p.Arg172Term |
122 | 138 | 6 | 0.01 | Severe | c.598C>T p.Gln200Term | |
123 | 139 | 2 | 2.1 | Severe | c.598C>T p.Gln200Term | |
124 | 140 | 12 | 0.9 | Severe | c.800G>A; p.Trp267Term | |
125 | 141 | 5 | 0.01 | Severe | c.814C>T; p.Gln272Term | |
126 | 142 | 4 | 2.1 | Severe | c.829C>T; Gln277Term | |
127 | 143 | 8 | 18 | Severe | c.998C>A; p.Ser333Term | |
144 | 2 | 10.1 | Severe | c.998C>A; p.Ser333Term | ||
128 | 145 | 3 | 0.18 | Severe | c.1010G>A; p.Trp337Term | |
129 | 146 | 3 | 4.4 | Severe | c.1010G>A; p.Trp337Term | |
130 | 147 | 1 | 0.07 | Severe | c.1288G>T; p.Glu430Term | |
131 | 148 | 6 | 0.01 | Severe | c.1340T>A; p.Leu447Term | |
132 | 149 | 3 | 0.01 | Severe | c.1375G>T; p.Glu459Term | |
133 | 150 | 3.5 | 0.01 | Severe | c.1445T>G; p.Leu482Term | |
134 | 151 | 6 | 0.01 | Severe | c.1608T>A;p.Tyr536Term | |
135 | 152 | 4 | 0.01 | Severe | IVS1 as A-G -2; c.104-2A>G | |
136 | 153 | 4 | 0.01 | Severe | IVS2 ds G-C +1; c.240+1G>C | |
137 | 154 | 4 | 4.8 | Severe | IVS2 ds G-T +1; c.240+1G>T | |
138 | 155 | 7 | 0.01 | Severe | IVS4 ds G-A +1; c.507+1G>A | |
139 | 156 | 16 | 3.96 | Severe | IVS4 ds G-A +1; c.507+1G>A | |
140 | 157 | 9 | 3.6 | Severe | IVS6 as A-G -2; c.880-2A>G | |
141 | 158 | 4 | 1.14 | Severe | IVS7 ds T-G +2c.1006+2T>G | |
142 | 159 | 5 | 0.01 | Severe | IVS7 as G-A -1; c.1007-1G>A | |
143 | 160 | 5 | 0.01 | Severe | IVS8 as C-A -15; c.1181-15C>A | |
144 | 162 | 6 | 2.1 | Severe | c.133delG p.Asp45Metfs | |
145 | 163 | 1.5 | 0.12 | Severe | c.248delT; p.Val83Glyfs | |
146 | 164 | 3 | 0.01 | Severe | c.305delT; p.Leu102Argfs | |
147 | 165 | 2 | 1.4 | Severe | c.404_405delAA; p.Lys135Serfs | |
148 | 166 | 2 | 2.52 | Severe | c.410_411delTT p.Phe137Sfs | |
149 | 167 | 6 | 4.2 | Severe | c.596_599delAACA;p.(Lys199Argfs) | |
150 | 168 | 9 | 0.58 | Severe | c.596_599delAACA;p.(Lys199Argfs) | |
151 | 169 | 7 | 1.2 | Severe | c.596_599delAACA;p.(Lys199Argfs) | |
152 | 170 | 5 | 9.1 | Severe | c.596_599delAACA;p.(Lys199Argfs) | |
153 | 171 | 4 | 0.7 | Severe | c.596_599delAACA;p.(Lys199Argfs) | |
154 | 172 | 3 | 18.1 | Severe | c.613delG; p.Ala205Profs | |
155 | 173 | 9 | 0.01 | Severe | c.667-683del17; p.Val223Thrfs | |
156 | 174 | 5 | 0.01 | Severe | c.687delC; p.His229Glnfs | |
157 | 175 | 6 | 2.3 | Severe | c.715_721del7; p.Gln239Cysfs | |
158 | 176 | 2 | 0.01 | Severe | c.782delC p.Pro261Lfs | |
159 | 177 | 13 | 0.66 | Severe | c.800_801delGG; p.Trp267Tyrfs | |
160 | 178 | 4 | 0.01 | Severe | c.899_900delAC; p.Tyr300Phefs | |
161 | 179 | 8 | 8.04 | Severe | c.908_909delCT; p.Ser303Cysfs | |
162 | 180 | 1 | 0.43 | Severe | c.1077delG; p.Ile360Tyrfs | |
163 | 181 | 12 | 12.6 | Severe | c.1129delC p.Leu377Phefs | |
164 | 182 | 4 | 0.01 | Severe | c.1191delC p.Met398Trpfs | |
165 | 183 | 6 | 0.01 | Severe | c.1214_1220del7 p.Leu406Hisfs | |
166 | 184 | 3 | 2.3 | Severe | c.1221delT p.Cys409Arg fs | |
167 | 185 | 16 | 0.79 | Severe | c.1353_1357delGTACCp.Tyr452Profs | |
168 | 186 | 3 | 2.4 | Severe | c.1431delT; p.Asp478Thrfs | |
169 | 187 | 3 | 1.9 | Severe | c.1466delG p.Val489Alafs | |
170 | 188 | 3 | – | 0.01 | Severe | c.776_777dupTA; p.Pro260Tyrfs |
171 | 189 | 5 | 0.01 | Severe | c.801_802insG; p.Met268Aspfs | |
172 | 190 | 4 | 1.3 | Severe | c.1151_1152 ins11; p.Phe384Leufs | |
173 | 191 | 9 | 6.6 | Severe | c.1239_1240insCT; p.Ala414Leufs | |
174 | 192 | 5 | 0.01 | Severe | c.1491_1492dupTA; p.Arg498Ileufs | |
175 | 193 | 4 | 2.64 | Severe | del c.104-1_104delGAinsT | |
176 | 194 | 8 | 0.01 | Severe | c.240+2_240+3 insTCCCAGA (intron 2) | |
177 | 195 | 4 | 0.48 | Severe | c.786-787delGGinsC; p.Ala263Profs | |
178 | 196 | 2 | – | 0.01 | Severe | gDNA level exons 1–3 deletion |
179 | 197 | 3 | – | 0.01 | Severe | gDNA level exons 1–3 deletion |
180 | 198 | 7 | 1.9 | Severe | gDNA level exons 1–4 deletion | |
181 | 199 | 4 | 0.01 | Severe | gDNA level exons 1–7 deletion | |
200 | 1 | 0.01 | Severe | gDNA level exons 1–7 deletion | ||
182 | 201 | 2 | 4.2 | Severe | gDNA level exon 4 deletion | |
183 | 202 | 5 | 0.01 | Severe | cDNA level del incl. ex 5–6 | |
184 | 203 | 2 | 9.6 | Severe | gDNA level exon 7 deletion | |
185 | 204 | 5 | 0.01 | Severe | Complete IDS del | |
205 | 3 | 0.01 | Severe | Complete IDS del | ||
186 | 206 | 2 | 1.3 | Severe | Complete IDS del | |
187 | 207 | 3 | 0.01 | Severe | Complete IDS del | |
188 | 208 | 7 | 0.01 | Severe | Complete IDS del | |
189 | 209 | 10 | 0.01 | Severe | Complete IDS del | |
190 | 210 | 3 | 0.01 | Severe | Complete IDS del | |
191 | 211 | 2 | 0.01 | Severe | Complete IDS del | |
192 | 212 | 5 | 0.01 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS-2 without exons deletion | |
193 | 213 | 2 | 0.01 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
194 | 214 | 3 | 0.01 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
195 | 215 | 6 | 2.5 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
196 | 216 | 6 | 7.2 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
197 | 217 | 6 | 0.43 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
198 | 218 | 3 | 2.4 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
199 | 219 | 3 | 0.01 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
220 | 13 | 3.6 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | ||
200 | 221 | 5 | 0.01 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
201 | 222 | 2 | 0.01 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
202 | 223 | 1 | 5.1 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
203 | 224 | 5 | 2.3 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
204 | 225 | 1 | 0.01 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS without exons deletion | |
205 | 226 | 3 | 0.01 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS with 3–7 exons deletion | |
206 | 227 | 2 | 0.01 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS with 3–7 exons deletion | |
207 | 228 | 3 | 0.12 | Severe | Recomb. between in. 7 and seq. distal of ex. 3 in IDS with 3–7 exons deletion |