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Table 1 Described mutations in the GLA gene found in suspected FD patients

From: Correlation between GLA variants and alpha-Galactosidase A profile in dried blood spot: an observational study in Brazilian patients

Aminoacid change (NM_000169.2)

Nucleotide change

Exon Location

Stop Codon Position

Type of alteration

Nr. of families

Enzymatic activity (μmol/L/h)

dbSNP

HGMD

Functional Characterization (%WT)

Likely Phenotype

Mean

Range

Pathogenic Mutations

 p.Q2*

c.4C>T

1

2

Nonsense

1

0.12

 

rs869312313

DM

No FC

Classical (dbFGP)

 p.Gly11AlafsTer110

c.32delG

1

110

Deletion

2

0.09

0 - 0.19

rs1057516967

DM

1.8±1.4 [19]

Classical (dbFGP; HGMD)

 p.A15E

c.44C>A

1

 

Missense

1

0.06

 

rs869312304

DM

0±0 [42]

Classical (dbFGP)

 p.A15G

c.44C>G

1

 

Missense

1

0.14

 

No dbSNP ID

DM

19±0.7 [36]

Classical (dbFGP)

 p.G35V

c.104G>A

1

 

Missense

1

0.15

 

No dbSNP ID

DM

No FC

Classical (HGMD)

 p.M42I

c.126G>A

1

 

Missense

1

0.17

 

No dbSNP ID

DM

No FC

Likely Classical (dbFGP) / Classical (HGMD)

 p.W47*

c.140G>A

1

47

Nonsense

1

+

 

No dbSNP ID

DM

No FC

Classical (dbFGP)

 p.R49C

c.145C>T

1

 

Missense

1

0.31

 

No dbSNP ID

DM

0±0 [19]

Classical (dbFGP; HGMD)

 p.R49G

c.145C>G

1

 

Missense

1

0

 

No dbSNP ID

DM

0±0 [19]

Classical (dbFGP)

 p.R49P

c.146G>C

1

 

Missense

1

0.25

 

rs398123205

DM

No FC

Classical (dbFGP; HGMD)

 p.C52*

c.156C>A

1

52

Nonsense

1

0.41

 

No dbSNP ID

DM

No FC

Classical (dbFGP; HGMD)

 p.F69L

c.207C>A

2

 

Missense

1

+

 

No dbSNP ID

DM

No FC

Mild/Late-onset - cardiac variant (dbFGP; HGMD)

 p.W81*

c.242G>A

2

81

Nonsense

1

+

 

rs398123208

DM

No FC

Classical (dbFGP; HGMD)

 p.C94Y

c.281G>A

2

 

Missense

2

0

 

rs113173389

DM

0±0 [19]

Classical (dbFGP; HGMD)

 p.R100K

c.299G>A

2

 

Missense

1

+

 

rs869312273

DM

0±0 [20]

Classical (dbFGP; HGMD)

 p.R112C

c.334C>T

2

 

Missense

5

0.25

0 - 1.25

rs104894834

DM

0±0 [20, 42]

Classical (dbFGP; HGMD)

 p.R112H

c.335G>A

2

 

Missense

3

0.17

0.03 - 0.28

rs869312273

DM

0±0 [20]; 1.6±0.6 [42]

Mild proteinuria -Later-onset (dbFGP; HGMD)

 p.F113L

c.337T>C

2

 

Missense

1

0.27

 

rs869312142

DM

17.3±3.6 [20]; 18.3±0.8 [36]

Later onset (dbFGP); Cardiac variant (HGMD)

 p.G132E

c.395G>A

3

 

Missense

1

0.01

 

No dbSNP ID

DM

0±0 [42]

Classical (dbFGP)

 p.C142R

c.424T>C

3

 

Missense

2

0

0 - 0.01

No dbSNP ID

DM

0±0 [20, 42]

Classical (dbFGP; HGMD)

 p.A156D

c.467C>A

3

 

Missense

2

0.16

0 - 0.33

rs869312307

DM

0±0 [42]

Classical (dbFGP)

 p.C172Y

c.515G>A

3

 

Missense

1

0.03

 

rs869312318

DM

0±0 [42]

Classical (dbFGP)

 p.M187T

c.560T>C

4

 

Missense

1

+

 

rs869312342

DM

0±0 [42]

Classical (dbFGP; HGMD)

 p.C202Y

c.605G>A

4

 

Missense

1

+

 

rs869312344

DM

0±0 [43]

Classical (dbFGP; HGMD)

 p.I198T

c.593T>C

4

 

Missense

1

0.15

 

rs727503950

DM

38.7±3.1 [43]

Later onset (dbFGP)

 p.W204*

c.611G>A

4

204

Nonsense

1

0.7

 

rs869312346

DM

No FC

Classical (dbFGP)

 p.N215S

c.644A>G

5

 

Missense

2

0.34

0.22 - 0.47

rs28935197

DM

15.6±1.0 [36] /15.7±2.4 [20] / 39.5±1.5 [43]

Later onset (dbFGP)

 p.R220*

c.658C>T

5

220

Nonsense

1

0.06

 

rs727503949

DM

0±0 [43]

Classical (dbFGP)

 p.W226*

c.677G>A

5

226

Nonsense

1

0.48

 

rs398123219

DM

No FC

Classical (dbFGP)

 p.R227*

c.679C>T

5

227

Nonsense

3

0.08

0.06 - 0.11

rs104894841

DM

No FC

Classical (dbFGP; HGMD)

 p.R227Q

c.680G>A

5

 

Missense

1

0

 

rs104894840

DM

0±0 [20, 42]

Classical (dbFGP; HGMD)

 p.Lys240Glufs*9

c.718_719delAA

5

248

Deletion

1

0.01

 

No dbSNP ID

DM

No FC

Classical (dbFGP)

 p.M267I

c.801G>A

5

 

Missense

1

0.17

 

rs869312408

DM

No FC

Classical (dbFGP; HGMD)

 p.V269M

c.805G>A

6

 

Missense

1

+

 

rs869312427

DM

0±0 [43]

Classical dbFGP; HGMD)

 p.V269A

c.806T>C

6

 

Missense

1

0.41

 

rs28935488

DM

9.0±1.4 [42]

Classical (dbFGP; HGMD)

 p.T282I

c.845C>T

6

 

Missense

1

0.05

 

No dbSNP ID

DM

5.0±0.5 [42] / 5.2±0.2 [36]

Classical (dbFGP)

 p.M290I

c.870G>A

6

 

Missense

10

0.31

0 - 0.60

rs869312438

DM

39±1.8 [42]

Later onset (dbFGP) - Classical (HGMD)

 p.A292V

c.875C>T

6

 

Missense

1

0.54

 

No dbSNP ID

DM

No FC

Classical (dbFGP)

 p.P293S

c.877C>T

6

 

Missense

1

0.10

 

rs869312440

DM

No FC

Classical (dbFGP)

 p.R301G

c.901C>G

6

 

Missense

1

0,34

 

rs398123224

DM

19±4.1 [42]

VUS (dbFGP)

 p.R301*

c.901C>T

6

301

Nonsense

2

0.06

0.01 – 0.11

rs398123224

DM

No FC

Classical (dbFGP) - Kidney disease (HGMD)

 p.Gln333Glufs*14

c.996_999delACAG

6

346

Deletion

2

1.84

 

rs398123229

DM

No FC

Classical (dbFGP; HGMD)

 p.R342Q

c.1025G>A

7

 

Missense

4

0.07

0 -0.14

rs28935493

DM

0±0 [20, 42]

Classical (dbFGP)

 p.Ser345Argfs*29

c.1033_1034delTC

7

373

Deletion

2

0.21

 

rs398123198

DM

No FC

Classical (dbFGP)

 p.W349*

c.1046G>A

7

349

Nonsense

1

0,45

 

No dbSNP ID

DM

No FC

Classical (dbFGP)

 p.R356W

c.1066C>T

7

 

Missense

17

0.47

0.19 - 1.62

rs104894827

DM

16.9±2.3 [42]

Later onset (dbFGP)

 p.R363H

c.1088G>A

7

 

Missense

3

0.43

0.13 - 0.72

rs111422676

DM

31.9±2.9 [42]

Later onset (dbFGP) - Renal presentation (HGMD)

 p.Y365*

c.1095T>A

7

365

Nonsense

3

0.06

0 - 0.13

rs104894849

DM

No FC

Classical (dbFGP)

 p.W399*

c.1196G>A

7

399

Nonsense

1

+

 

No dbSNP ID

DM

2% [21]

Classical (dbFGP; HGMD)

 p.Thr412Serfs*?

c.1235_1236delCT

7

late termination codon

Deletion

1

0

 

rs797044777

DM

No FC

Classical (dbFGP; HGMD)

Variants of Unknown Significance

 p.E66Q

c.196G>C

2

 

Missense

1

+

 

rs104894833

DFP

52.0±1.3 [36]

Benign (dbFGP)

 p.R118C

c.352C>T

2

 

Missense

30

1.68

1.15 - 2.10

rs148158093

DM

24.0±1.3 [36]

Benign (dbFGP); Cardiac variant (HGMD)

 p.A143T

c.427G>A

3

 

Missense

8

1.04

0.58 - 1.86

rs104894845

DM

31.3±5.6 [42]

Benign (dbFGP)

 p.R220Q

c.659G>A

5

 

Missense

1

1.17

 

rs727503949

DM?

104±11.3 [42]

Likely bening (dbFGP)

 p.N228S

c.683A>G

5

 

Missense

1

2.03

 

rs869312152

DM

59.5±9.8 [43] / 124.5±4.1 [36]

Likely benign (dbFGP)

 p.D313Y

c.937G>T

6

 

Missense

38

1.65

0.72 - 2.10

rs28935490

DM?

83.9±21.1 [42]

Benign (dbFGP)

 p.R356Q

c.1067G>A

7

 

Missense

1

0.9

 

rs869312163

DM

89.1±5.0 [42] / 36.1±1.5 [36]

Later onset (dbFGP)

 p.A368T

c.1102G>A

7

 

Missense

1

1.69

1.69

rs144994244

DM?

103.7±33.6 [42]

Benign (dbFGP)

  1. F Female, M Male, No FC No functional characterization, NA Not Applicable, VUS Variant of Unknown Significance, DM Disease Causing Mutation, DM? Disease Causing Mutation?, DFP disease-associated polymorphism with supporting functional evidence, dbFGP (International Fabry Disease Genotype-Phenotype Database http://dbfgp.org/dbFgp/fabry/); DBS enzymatic activity applicable only for male: for samples screened by LEIM-UNIFESP the result is show as μmol/L/h; for samples screened by other laboratories, the result is show as + (positive)