Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis

Table 1

Clinical phenotypes of DH patients with detected variants.

Patient ID

Age, sex

Birth weight (g)

Gestational age (week + day)

Thyroid widths (cm) (age)

Transient or permanent CH

Screening TSH (μIU/ml)

At confirmative diagnosis, before Tx

Severity

Gene

Variants

Age

TSH (μIU/ml)

FT4 (ng/dl)

Nonpolymorphic

Polymorphic

1

2y, M

3550

39 + 6

1.9 (20 d)

NA

15

20 d

80.08

0.84

Mild

DUOX2

p.K530X, p.R1211H

p.H678R, p.S1067L

DUOXA2

p.R133H

2

1 y and 10 m, M

3300

37

1.2 (37 d)

NA

33.1

34 d

58.27

0.86

Mild

DUOX2

p.R434_S440del, p.R885Q

3

3 y and 6 m, M

3400

39 + 6

1 (29 d)

NA

129

29 d

>100

0.38

Moderate

DUOX2

p.S906P, p.L1160del

4

3 y, F

3900

39 + 1

1.4 (23 d)

NA

122

23 d

>100

0.2

Severe

5

2 y and 3 m, F

3320

39 + 6

1.4 (27 d)

NA

116

27 d

45.27

0.9

Mild

DUOX2

p.V779M, p.G1513R

6

4 y and 7 m, F

4440

41

1.1 (8 m)

Permanent

117

35 d

>100

0.32

Moderate

DUOXA2

p.Y138X (Hom), p.Y246X

7

4 y, F

3400

39 + 4

1.1 (29 d)

NA

318

29 d

>100

0.15

Severe

DUOX2

p.K530X, p.R1110Q

p.H678R, p.S1067L (Hom, CC)

8

5 y and 1 m, F

3100

40

2 (3 6d)

Permanent

56.1

32 d

>100

0.16

Severe

DUOX2

p.K530X, p.R1110Q

p.H678R, p.S1067L (Hom, CC)

9

4 y, F

3365

39

1.3 (16 d)

Permanent

11

17 d

>100

0.3

Severe

DUOX2

p.D435G, p.R1110Q

p.S1067L

10

5 y and 6 m, M

3900

40 + 6

1.16 (52 d)

Transient

39

25 d

39.35

0.61

Moderate

DUOX2

p.K530X, p.R885Q

p.H678R, p.S1067L

11

4 y and 5 m, F

3100

40 + 2

1.08 (47 d)

NA

23.2

33 d

39.73

0.89

Mild

DUOX2

p.M927V (Hom)

TG

p.C687LfsX34

12

1 y and 6 m, F

3800

39 + 1

1.17 (29 d)

NA

69.3

30 d

>100

0.35

Moderate

DUOX2

p.G1513R

TG

p.G505D

13

1 y and 6 m, M

4050

40 + 1

1.1 (33 d)

NA

161

33 d

16.16

0.96

Mild

DUOX2

p.G1521X

14

4 y and 1 m, F

1600

34 + 2

1 (2 m)

NA

33.6

69 d

37.53

0.93

Mild

DUOX2

p.R885Q, IVS28+1G>T

15

1 y and 4 m, F

3970

40 + 6

1.5 (26 d)

NA

32.9

27 d

100

0.49

Moderate

DUOX2

p.R432H, p.A1323T, p.L1343F

p.H678R, p.S1067L

16

1 y and 3 m, M

3700

39 + 1

1.3 (23 d)

NA

80

23 d

100

0.14

Severe

DUOX2

p.P76L, p.R683L, p.L1343F

p.H678R, p.S1067L

TG

p.S1139L

17

1 y and 2 m, F

3700

40 + 2

2.8 (33 d)

NA

9.12

33 d

>100

0.28

Severe

DUOXA2

p.Y246X

SLC26A4

p.A429E

TG

IVS10-1G>A

18

5 y and 11 m, M

4600

40 + 6

1.1 (2 m)

Permanent

100

28 d

100

0.1

Severe

DUOX2

p.R1110Q (Hom)

19

1 y and 5 m, M

3200

39 + 2

1.4 (42 d)

NA

12.4

37 d

14.5

1.21

Mild

DUOX2

p.R1110Q, IVS28+1G>T

p.S1067L

20

1 y and 3 m, F

2200

34 + 1

1.1 (36 d)

NA

14.9

37 d

14.9

0.51

Moderate

DUOX2

IVS17+1G>T

p.H678R, p.S1067L

TG

p.G1456R

21

1 y and 2 m, F

3400

40

1.1 (28 d)

NA

11.7

28 d

64.28

0.55

Moderate

DUOX2

p.H678R, p.S1067L

Normal

0–8

0–8

0.93–1.7

Neuropsychological development was low; parental DNA sample available; m: month; d: day; y: year; F: female; M: male; CH: congenital hypothyroidism; TSH: thyroid-stimulating hormone; FT4: free tetraiodothyronine; Tx: L-thyroxine; Hom: homozygous; NA: data not available.