Table 4.
The five most commonly reported variants among patients by phenotypic subgroup across the clinical spectrum of Pompe disease globally and by geographic region
| Group A a | Group B b | Group C c | |||
|---|---|---|---|---|---|
| DNA | Protein | DNA | Protein | DNA | Protein |
| Global | |||||
| N = 373 variants | N = 459 variants | N = 1,243 variants | |||
| c.2560C>T (n = 28) | p.(Arg854Ter) | c.‐32‐13T>G (n = 128) | p.? | c.‐32‐13T>G (n = 561) | p.? |
| c.1935C>A (n = 27) | p.(Asp645Glu) | c.2481+102_2646+31del (n = 20) | p.(Gly828_ Asn882del) | c.525del (n = 71) | p.(Glu176ArgfsTer45) |
| c.525del (n = 21) | p.(Glu176ArgfsTer45) | c.525del (n = 19) | p.(Glu176ArgfsTer45) | c.2481+102_2646+31del (n = 46) | p.(Gly828_ Asn882del) |
| c.2481+102_2646+31del (n = 14) | p.(Gly828_Asn882del) | c.2238G>C (n = 18) | p.(Trp746Cys) | c.2238G>C (n = 20) | p.(Trp746Cys) |
| c.1726G>A (n = 11) d | p.(Gly576Ser) | c.307T>G (n = 9) | p.(Cys103Gly) | c.307T>G (n = 18) | p.(Cys103Gly) |
| Europe | |||||
| N = 125 variants | N = 245 variants | N = 822 variants | |||
| c.525del (n = 12) | p.(Glu176ArgfsTer45) | c.‐32‐13T>G (n = 88) | p.? | c.‐32‐13T>G (n = 398) | p.? |
| c.2481+102_2646+31del (n = 9) | p.(Gly828_Asn882del) | c.2481+102_2646+31del (n = 11) | p.(Gly828_ Asn882del) | c.525del (n = 55) | p.(Glu176 ArgfsTer45) |
| c.2237G>A (n = 7) | p.(Trp746Ter) | c.525del (n = 9) | p.(Glu176 ArgfsTer45) | c.2481+102_2646+31del (n = 25) | p.(Gly828_ Asn882del) |
| c.2560C>T (n = 7) | p.(Arg854Ter) | c.307T>G (n = 8) | p.(Cys103Gly) | c.307T>G (n = 14) | p.(Cys103Gly) |
| c.1933G>A (n = 5) | p.(Asp645Asn) | c.1933 G>A (n = 5) | p.(Asp645Asn) | c.1655T>C (n = 10) | p.(Leu552Pro) |
| North America | |||||
| N = 172 variants | N = 148 variants | N = 342 variants | |||
| c.2560C>T (n = 19) | p.(Arg854Ter) | c.‐32‐13T>G (n = 40) | p.? | c.‐32‐13T>G (n = 154) | p.? |
| c.525del (n = 9) | p.(Glu176ArgfsTer45) | c.525del (n = 10) | p.(Glu176 ArgfsTer45) | c.2481+102_2646+31del (n = 21) | p.(Gly828_ Asn882del) |
| c.2297A>C (n = 6) | p.(Tyr766Ser) | c.2481+102_2646+31del (n = 9) | p.(Gly828_ Asn882del) | c.525del (n = 16) | p.(Glu176 ArgfsTer45) |
| c.1799G>A (n<5) | p.(Arg600His) | c.2560C>T (n = 5) | p.(Arg854Ter) | c.1655T>C (n = 5) | p.(Leu552Pro) |
| c.1844G>A (n<5) | p.(Gly615Glu) | c.1082C>T (n<5) | p.(Pro361Leu) | c.2560C>T (n = 5) | p.(Arg854Ter) |
| Asia‐Pacific | |||||
| N = 62 variants | N = 58 variants | N = 69 variants | |||
| c.1935C>A (n = 26) | p.(Asp645Glu) | c.2238G>C (n = 15) | p.(Trp746Cys) | c.2238G>C (n = 19) | p.(Trp746Cys) |
| c.1726G>A (n = 11) d | p.(Gly576Ser) | c.2662G>T (n = 5) | p.(Glu888Ter) | c.1935C>A (n = 7) | p.(Asp645Glu) |
| c.1411_1414del (n<5) | p.(Glu471ProfsTer5) | c.1634C>T (n<5) | p.(Pro545Leu) | c.1726G>A (n<5) d | p.(Gly576Ser) |
| c.1843G>A (n<5) | p.(Gly615Arg) | c.1935C>A (n<5) | p.(Asp645Glu) | c.1822C>T (n<5) | p.(Arg608Ter) |
| c.1465G>A (n<5) | p.(Asp489Asn) | c.1726G>A (n<5) d | p.(Gly576Ser) | c.1843G>A (n<5) | p.(Gly615Arg) |
| Latin America | |||||
| N<5 variants | N<5 variants | N = 10 variants | |||
| c.2560C>T (n<5) | p.(Arg854Ter) | c.1556T>C (n<5) | p.(Met519Thr) | c.‐32‐13T>G (n = 7) | p.? |
| c.1912G>T (n<5) | p.(Gly638Trp) | c.1408_1410del (n<5) | p.(Asn470del) | c.1465G>A (n<5) | p.(Asp489Asn) |
| c.2481+102_2646+31del (n<5) | p.(Gly828_Asn882del) | — | — | c.1832G>A (n<5) | p.(Gly611Asp) |
| — | — | — | — | c.2560C>T (n<5) | p.(Arg854Ter) |
| Middle East | |||||
| N = 10 variants | N<5 variants | N = 0 | |||
| c.340_341insT (n = 6) | p.(Lys114fsTer32) | c.1064T>C (n<5) | p.(Leu355Pro) | — | — |
| c.2015G>A (n<5) | p.(Arg672Gln) | c.1210G>A (n<5) | p.(Asp404Asn) | — | — |
| c.1799G>A (n<5) | p.(Arg600His) | c.2015G>A (n<5) | p.(Arg672Gln) | — | — |
| c.2056_2057delinsCC (n<5) | NA | c.2105G>A (n<5) | p.(Arg702His) | — | — |
Note. Variant frequencies reported in the Pompe Registry in fewer than five patients are reported as < 5 to protect patient privacy.
Group A: Onset of symptoms ≤ 12 months of age with cardiomyopathy (patients classified as classic infantile Pompe disease). Group A also may include a subset of patients with less severe cardiomyopathy and slower disease progression.
Group B: Onset of symptoms ≤ 12 years of age (includes patients with onset of symptoms ≤ 12 months of age without cardiomyopathy and not included in Group A).
Group C: Onset of symptoms > 12 years of age.
c.1726G>A is a well‐known pseudodeficiency variant and is linked to other variants (see main text).