Table 1.
Mutations of the iduronate-2-sulfatase (IDS) gene underlying Taiwanese Hunter syndrome by sequencing analysis.
| No. | Missense Nucleotide Alteration | Protein Alteration | Gene Location | Phenotype Severity | IDS Activity | uGAG Tests | Known/ Novel |
ACMG Classification |
|---|---|---|---|---|---|---|---|---|
| 1 | c.137A>C | p.D46A | Exon 2 | S | 0.1 | Positive | Known [16] | |
| 2 | c.142C>T | p.R48C | Exon 2 | #NBS | 16.27 | Negative | Novel | Likely Pathogenic |
| 3 | c.189T>G | p.N63K | Exon 2 | S | 0.21 | Positive | Known [17] | |
| 4 | c.253 G>A | p.A85T | Exon 3 | A | 0.00 | Positive | Known [17,18] | |
| 5 | c.254C>T | p.A85V | Exon 3 | #NBS | 0.83 | Positive | Novel | Likely Pathogenic |
| 6 | c.262C>T | p.R88C | Exon 3 | S | 0.43 | Positive | Known [17,19,20] | |
| 7 | c.301C>T | p.R101C | Exon 3 | #NBS | 15.4-40.8 | Negative | Known [21] | Benign |
| 8 | c.311A>T | p.D104V | Exon 3 | #NBS | 0.32 | Positive | Novel | Likely Pathogenic |
| 9 | c.413A>G | p.H138R | Exon 3 | S | 0.18 | Positive | Known [17] | |
| 10 | c.454A>C | p.S152R | Exon 4 | S | 0.11 | Positive | Novel | Likely Pathogenic |
| 11 | c.589C>T | p.P197S | Exon 5 | #NBS | 7.8 | Negative | Novel | Likely Pathogenic |
| 12 | c.683C>T | p.P228L | Exon 5 | A | 0.56 | Positive | Known [17,22] | |
| 13 | c.697A>G | p.R233G | Exon 5 | A | 0.71 | Positive | Known [20] | |
| 14 | c.778C>T | p.P260S | Exon 6 | #NBS | 6.47 | Negative | Novel | Likely Pathogenic |
| 15 | c.797C>G | p.P266R | Exon 6 | A | 1.96 | Positive | Known [22] | |
| 16 | c.801 G>T | p.W267C | Exon 6 | A | 0.89 | Positive | Known [17] | |
| 17 | c.817C>T | p.R273W | Exon 6 | #NBS | 0.2 | Positive | Novel | Likely Pathogenic |
| 18 | c.851C>T | p.P284L | Exon 6 | #NBS (A) | 0.51 | Negative | Known [24] | Uncertain Significance |
| 19 | c.890G>A | p.R297H | Exon 7 | #NBS | 9.2 | Negative | Novel | Likely Pathogenic |
| 20 | c.998C>T | p.S333L | Exon 7 | S | 0.34 | Positive | Known [25,26] | |
| 21 | c.1025A>G | p.H342R | Exon 8 | #NBS | 0.4 | Positive | Novel | Likely Pathogenic |
| 22 | c.1039A>G | p.K347E | Exon 8 | S | 0.49 | Positive | Known [17] | |
| 23 | c.1400C>T | p.P467L | Exon 9 | #NBS | 0.27 | Positive | Known [27,28] | Likely Pathogenic |
| 24 | c.1402C>T | p.R468W | Exon 9 | S | 0.04 | Positive | Known [17,29] | |
| 25 | c.1403G>A | p.R468Q | Exon 9 | S | 0.00 | Positive | Known [17,21,30] | |
| 26 | c.1454T>G | p.I485R | Exon 9 | S | 0.16 | Positive | Known [17,31] | |
| 27 | c.1466G>A | p.G489D | Exon 9 | S | 0.11 | Positive | Known [17] | |
| 28 | c.1478G>A | p.R493H | Exon 9 | #NBS | 8.82–124.91 | Negative | Novel | Likely Pathogenic |
| 29 | c.1478G>C | p.R493P | Exon 9 | S | 0.13 | Positive | Known [16,28] | |
| 30 | c.1499C>T | p.T500I | Exon 9 | #NBS | 13.2–34.5 | Negative | Novel | Benign |
| 31 | c.1513T>C | p.P505L | Exon 9 | #NBS | 5.93 | Negative | Novel | Likely Pathogenic |
| 32 | c.1600A>C | p.N534H | Exon 9 | A | 1.09 | Positive | Known [32] | |
| Nonsense | ||||||||
| 1 | c.801G>A | p.W267X | Exon 6 | S | 0.15 | Positive | Known [17] | |
| 2 | c.1106C>G | p.S369X | Exon 7 | A | 0.1 | Positive | Known [33] | |
| 3 | c.1561G>T | p.E521X | Exon 9 | S | 0.24 | Positive | Known [17,34] | |
| Silent | ||||||||
| 1 | c.684A>G | p.Pro228 = | Exon 5 | #NBS | NA | NA | Novel | Benign |
| 2 | c.1122 C>T | p.Gly374 = | Exon 8 | A | 0.34–7.1 | Positive | Known [20] | |
| Splicing | ||||||||
| 1 | c.103 + 34_56dup | Intron 1 | #NBS | 0.56–14.69 | Negative | Novel | Uncertain Significance | |
| 2 | c.240 + 1G>C | False splicing; deletion of 105 AAs | Intron 2 | S | 0.68 | Positive | Known [17] | |
| 3 | c.708 + 2T>G | − | Intron 5 | S | 0.48 | Positive | Known [22] | |
| 4 | c.880-2A>T | − | Intron 7 | A | 0.75 | Positive | Novel | Pathogenic |
| 5 | c.1006 + 5G>C | Splicing in 22 nucleotide | Intron 7 | A | 0.05 | Positive | Known [35] | |
| 6 | c.1180 + 184T>C | − | Intron 8 | #NBS | NA | NA | Novel | |
| Small Deletions | ||||||||
| 1 | c.231_236delCTTTGC | Loss of F78 and A79 | Exon 2 | S | 0.12 | Positive | Known [17] | |
| 2 | c.1055del12 | Loss of V353-H356 | Exon 8 | S | 0.25 | Positive | Known [17] | |
| 3 | c.1184delG | Frame shift, 44 altered AAs, term | Exon 9 | S | 0.19 | Positive | Known [17] | |
| 4 | c.1421delAG | Frame shift, 7 altered AAs, term | Exon 9 | S | 0.34 | Positive | Known [17] | |
| Gross deletions | ||||||||
| 1 | Exon 4–7 deletion | NA | A | 0.3 | Positive | Known [11] | ||
| 2. | c.1007-1666_c.1180 + 2113 delinsTT | NA | #NBS | 0.99 | Positive | Known [36,37] | Pathogenic | |
| 3 | Exon 8 deletion | NA | A | 0.64 | Positive | Known [37] | ||
| Complex Rearrangements | ||||||||
| 1 | IDS inversion | NA | A | 0.13–1.54 | Positive | Known [38,39] |
A combination of four mutations, including c.103 + 34_56dup, c.851C>T; p.P284L, c.1180 + 184T>C, and c.684A>G; p.Pro228 =. # NBS is the abbreviation of newborn screening; S: Severe; A: Attenuated.