Table 2.
Mutations of the iduronate-2-sulfatase (IDS) gene found in suspected MPS II infants referred from newborn screening program for MPS in Taiwan.
| No. | Missense Nucleotide Alteration/Protein Alteration |
Ages (Ms) of the Test | Ages (Yrs) at last Follow up | (a)Leukocyte IDS Activity | (b)uGAG Tests | DMB/Cre Ratio | uDS (μg/mL) |
uHS (μg/mL) |
ACMG Classification |
|---|---|---|---|---|---|---|---|---|---|
| 1 | c.142C>T; p.R48C | 1.7 | 0.3 | 16.27 | Negative | 38.73 | 0.01 | 0.75 | Likely Pathogenic |
| 2 | c.254C>T; p.A85V | 4.6 | 0.5 | 0.83 | Positive | 78.58 | 11.59 | 12.36 | Likely Pathogenic |
| 3 | c.301C>T; p.R101C | 1.7 | 3.4 | 15.4–40.8 | Negative | 5.07 | 0.2 | 0.13 | Benign |
| 4 | c.311A>T; p.D104V | 0.9 | 0.3 | 0.32 | Positive | 44.6 | 45.95 | 11.43 | Likely Pathogenic |
| 5 | c.589C>T; p.P197S | 1.9 | 3 | 7.80 | Negative | 63.82 | 0.38 | 1.46 | Likely Pathogenic |
| 6 | c.778C>T; p.P260S | 2.3 | 1 | 6.47 | Negative | 12.29 | 0.12 | 0.1 | Likely Pathogenic |
| 7 | c.817C>T; p.R273W | 0.9 | 0.7 | 0.20 | Positive | 65.06 | 15.78 | 16.23 | Likely Pathogenic |
| 8 | c.851C>T; p.P284L | 1.8 | 1.3 | 0.51 | Negative | 34.22 | 0.03 | 0.08 | Uncertain Significance |
| 9 | c.890G>A; p.R297H | 3 | 0.5 | 9.20 | Negative | 69.67 | 0.08 | 0.04 | Likely Pathogenic |
| 10 | c.1025A>G; p.H342R | 1.6 | 0.3 | 0.40 | Positive | 70.90 | 21.21 | 12.06 | Likely Pathogenic |
| 11 | c.1400C>T; p.P467L | 1.9 | 0.7 | 0.27 | Positive | 153.16 | 21.4 | 30.01 | Likely Pathogenic |
| 12 | c.1478G>A; p.R493H | 1.6 | 3.2 | 26.37 ± 10.98 | Negative | 40.18 | 0.04 | 0.09 | Likely Pathogenic |
| 13 | c.1499C>T; p.T500I | 1.6 | 1.9 | 17.15 ± 3.69 | Negative | 26.11 | 0.1 | 0.27 | Benign |
| 14 | c.1513T>C; p.P505L | 1.4 | 0.5 | 5.93 | Negative | 32.15 | 0.08 | 0.11 | Likely Pathogenic |
| Splicing | |||||||||
| 15 | * c.103 + 34_56dup | 1.1 | 3.8 | 3.86 ± 2.24 | Negative | 41.15 | 0.06 | 0.11 | Uncertain Significance |
| 16 | c.1180 + 184T>C | NA | NA | NA | NA | NA | |||
| Gross Deletions | |||||||||
| 17 | c.1007-1666_c.1180 + 2113 delinsTT (including exon 8 del) | 1.2 | 1.2 | 0.99 | Positive | 177.96 | 30.77 | 203.35 | Pathogenic |
| Complex Rearrangement | |||||||||
| 18 | IDS inversion | 1.5 | 0.3 | 0.13 | Positive | 44.05 | 8.72 | 37.30 |
(a) IDS enzyme activity (Ref. 12.89 ~ 131.83 μmol/g protein/4 h); (b) GAG tests including GAG quantification (DMB/Cre ratio): Reference values 39.9 ± 13.1 mg/mmol creatinine (< 6 months), 44.6 ± 23.7 (under 2 years old), 15.3 ± 13.0 (2–17 years old), 5.2 ± 2.5 (18–42 years old); 2-dimensional electrophoresis: Showing DS and HS patterns rather than CS; and the quantitative analyses of GAG-derived disaccharides (DS and HS) using tandem mass spectrometry assay (MS/MS-based method), cut-off values: < 0.80 μg/mL for DS; < 0.78 μg/mL for HS. *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 = (n = 99).