Table 1.
Summary of Previously Reported TSHβ Gene Mutations: Clinical Information and Biochemical Profile
| Gene mutation/protein change | Family/patient ID | Ethnic origin | Inbred | Sex | Neonatal TSH (mIU/L) | Basal TSH (mIU/L) | Peak TSH response to TRH stimulation (mIU/L) | TSH assay | Serum iodothyronine levels (normal range)a | Ref |
|---|---|---|---|---|---|---|---|---|---|---|
| c.313delT C105Vfs114Xb |
Irish-Scottish | No | F | 0.2 | 0.09 | 1.33 | RIA | <0.1 ng/dL | (9) | |
| F | <0.1 | 0.93 | 1.61 | <0.1 ng/dL | ||||||
| Fam A | Swiss | No | M | Normal (DELFIA, Wallac) | 0.02 | 0.03 | Na | 1.8 pmol/L (12–26) | (10) | |
| Fam B | Swiss | No | M | Normal (DELFIA) | 0.03 | 0.05 | 2.5 pmol/L (12–26) | |||
| Fam C | Argentinian | No | Na | Na | <0.04 | Na | Low or ND | |||
| Fam D | Argentinian | No | Na | Na | <0.04 | Na | Low or ND | |||
| Fam E | Argentinian | No | Na | Na | <0.04 | Na | Low or ND | |||
| German | No | F | 0.01 | 23.8/0.08 | 0.1 | Assay unknown Elecsys, Roche |
6.4 pmol/L (12–22) | (11) | ||
| S.A. | Argentinian | Yes | M | Na | 0.04 | 0.65 | Elecsys, Roche | T4 1.4 μg/dL (6.0–14) | (12) | |
| V.T. | Argentinian | No | F | Na | 0.07 | 0.29 | T4<1 μg/dL fT4 0.26 ng/dL (0.8–2.20) |
|||
| M.A. | Argentinian | Yes | F | Na | 0.77 | Na | T4<1, fT4 0.1 | |||
| B.N. | Argentinian | No | F | Na | 0.1 | Na | T4 4.6, fT4 0.06 | |||
| B.L. | F | Normal | 0.8 | 1.4 | T4<1, fT4 0.2 | |||||
| B.F. | Argentinian | No | M | Normal | 0.19 | 0.39 | T4<1 | |||
| K.G.A. | Argentinian | No | M | Normal | 0.21 | Na | T4<1 | |||
| D.D. | Argentinian | No | F | Normal | 0.03 | Na | T4<1, fT4<0.06 | |||
| German | No | F | Normal (DELFIA) | <0.04 | <0.04 | IRMAmat, Byk-Sangtec Diagnostica and Amerlite | T4<0.4 μg/dL (5.2–12.6) | (13) | ||
| Fam A | German | No | F | Normal, <15 | 0.15 | Na | Na | fT4 ND | (14) | |
| F | Normal, <15 | 0.06 | Na | T4 24 μg/L (89–236) | ||||||
| fam C | German | No | M | Na | 0.3 | Na | T4 5 μg/L (59–163) | |||
| F | Normal | 0.02 | Na | fT4 2 ng/L (15–30) | ||||||
| German | No | M | 1.3 | 0.4 0.07 |
Na | DELFIA, Wallac ELISA, Boehringer | T4 10.2 nmol/L | (15) | ||
| II1 | Polish | ? | M | 0.04 | 0.03 | No response | Na | fT4 4.24 pmol/L | (16) | |
| II2 | F | 0.01 | 1.9 | Na | fT4<2.5 pmol/L | |||||
| II3 | F | 0.1 | 0.1 | Na | fT4 2.5 pmol/L | |||||
| Pt 2 comp het (see C88Y) | Argentinian | No | M | Normal | 0.5 | 0.52 | Na | T4 12.9 nmol/L (103–172) fT4 10 pmol/L (17–24) |
(17) | |
| Comp het (see F57fs62X) | Irish-Native American/German | No | M | TSH<20 T4 45 nmol/L (>83) |
0.06 | <0.005 | Abbott Architect i2000 | fT4<2.6 pmol/L (10–28.1) | (18) | |
| American | No | M | Na | <0.01 | No response | Na | fT4<0.5 ng/dL (0.7–2.7) | (19) | ||
| F | Abnormal | <0.01 | Na | fT4 2.4 ng/dL (on L-T4) | ||||||
| Belgian | No | F | 13.5 (RIA) T4 3.6 μg/dL (5.6–11.4) |
14.8 <0.03 0.2 1.9 |
18.2 0.07 0.3 4.1 |
RIA, Amersham ICMA ACS 180 IRMA Nichols Polyclonal RIA |
T4 0.3 μg/dL (5.6–11.4) fT4<0.2 μg/dL (0.8–2.0) |
(20) | ||
| Fam A,V-3 | Brazilian | Yes | F | Na | 0.8 | 1.7 | Nicholas Institute | T4 0.5 μg/dL (5–12) | (21) | |
| Fam A,V-4 | F | Na | 0.02 | 0.8 | T4 0.5 μg/dL | |||||
| Fam A,V-6 | M | Na | 0.3 | 0.9 | T4 0.5 μg/dL | |||||
| Fam B,V-8 | Brazilian | Yes | F | Na | 0.1 | 1.6 | T4 0.5 μg/dL | |||
| Pt Z1 | Swiss | ? | F | Normal (DELFIA) | 23.4 | Na | ST AIA-Pack TSH, Tosoh | fT4<1 pmol/L (10.3–29.7) | (22) | |
| Pt N1 comp het (Q49X) | French | ? | M | Normal (DELFIA) | 0.76 | Na | AxSYM hTSH ultrasensitive II, Abbott Or IRMAmat TSH, Byk Sangtec Diagnostica Or HYPERSENSITIVE hTSH, Beckman Coulter |
fT4 0.7 pmol/L | ||
| Pt D1 | German | ? | F | Normal (DELFIA) | ND | Na | undetectable | |||
| Pt D2 | F | 0.013 | 0.013 | Na | fT4 7.59 pmol/L | |||||
| Pt P1 | Portugese | ? | M | Normal (DELFIA) | 0.1 | Na | T4 59 nmol/L (78.5–151.9) | |||
| Pt P2 | M | Normal (DELFIA) | 0.15 | Na | T4 34.7 nmol/L fT4 4.1 pmol/L |
|||||
| c.145G>A G29R |
Japanese | Yes | F | Na | <0.1 | <0.1 | IRMA, Daiichi Radioisotope | Na | (6,7,23) | |
| F | Na | <0.1 | <0.1 | Na | ||||||
| Fam 2 | Japanese | Yes | F | Na | Na | Na | Na | Na | (24) | |
| Fam 3 | Japanese | Yes | M | Na | Na | Na | Na | Na | ||
| Japanese | No | M | Na | 0.5 | No response | Na | T4 2.53 μg//dL fT4I 0.84 |
(25) | ||
| IVS2+5;G- >A Abnormal splicing Skipping ex2 |
? | Yes | F | Na | 0.19<0.03 (on L-T4) | Na | ECLIA, Roche CLIA, Chiron Corp |
fT4 1.4 pmol/L (10–22) | (26) | |
| Fam A | Turkish | Yes | M | Normal, <15 | 0.23 0.047 0.043 |
0.35 | Chiron Diagnostics Elescys, Roche Corning, Nichols diagnostics | fT4 0.2 ng/dL (1–2.6) | (27) | |
| Fam B,II-1 | Turkish/ Kurdish | Yes | M | Na | 0.19 | 0.02 | Chiron Diagnostics | T4 1 μg/dL (4.5–12.5) | ||
| Fam B, II-3 | F | Na | 0.2 | Na | T4 1 μg/dL | |||||
| Fam B, II-4 | M | Na | 0.3 | Na | T4 1 μg/dL | |||||
| c.162G>A Abnormal splicing Skipping ex2 |
Pt 1 | Argentinian | No | M | Normal | 1.07 | 1.83 | Na | T4<12.9 nmol/L (103–172) fT4<2.57 pmol/L (17–24) |
(17) |
| c.94G>T E12X |
FamA, II-1 | Greek | Yes | M | Normal | Low | Na | RIA | T4 0.2 μg/dL | (28) |
| FamA, II-2 | F | Normal | Low | No response | T4 0.1 μg/dL | |||||
| FamB, II-1 | Greek | Yes | M | Normal | Low | No response | T4 0.9 μg/dL | |||
| c.205C>T Q49X |
II-1 | Turkish | Yes | F | Na | 0.02 | 0.07 | Na | T4 1.29 nmol/L (57.9–140.3) fT4 1.29 pmol/L (10.3–19.3) |
(29) |
| II-2 | M | Na | 0.01 | 0.01 | T4 10.42 nmol/L fT4 2.57 pmol/L |
|||||
| FamB, Pt 1 | Greek/Uzbekistan | ? | M | Na | 0.03 | No response | MEIA (IMX, Abbott) | T4 0.003 μg/dL (7.2–15.7) | (30) | |
| FamB, Pt 2 | M | Na | 4 | 6 | T4 1 μg/dL | |||||
| II-1 | Greek/Armenian | Yes | F | 1.64 (2nd generation ELIA, Roche) | <0.05 | Na | 3rd generation, Beckman | fT4 1.1 pmol/L (7.5–21.1) | (16) | |
| II-2 | F | 1.43 (2nd generation ELIA, Roche) | <0.05 | Na | fT4 1.5 pmol/L (7.5–21.1) | |||||
| Egyptian | Yes | F | Na | 3.74 3.46 2.55 <0.002 0.02 |
4.8 ND ND |
ELISA, ES600, Roche IFMA, Delfia ECLIA, Elecsys IRMA, Myria, Bouty IFMA, DelfiaUltra |
fT4 2.6 pmol/L (9–20) | (31) | ||
| pt N1 comp het (C105Vfs114X) | French | ? | M | Na | 0.76 | IRMAmat TSH, Byk, Sangtec Diagnostica | fT4 0.7 pmol/L | (22) | ||
| c.313T>C C85R |
FamA, Pt 1 | Greek | ? | F | Na | 0.1 | 0.1 | MEIA (IMX, Abbott) | T4 5.1 μg/dL (5–12.5) | (30) |
| c.323G>A C88Y |
Pt 2 comp het (C105Vfs114X) | Argentinian | No | M | Normal | 0.5 | 0.52 | Na | T4 12.9 nmol/l (103–172) fT4 10 pmol/L (17–24) |
(17) |
| c.229delT F57fs62X |
Comp het (C105Vfs114X) | Irish-Native American/German | No | M | TSH<20 T4 45 nmol/L (>83) |
0.06 | <0.005 | Abbott Architect i2000 | fT4<2.6 pmol/L (10–28.1) | (18) |
a
Clinical hypothyroidism was documented in all individuals.
b
The signal peptide is included in this mutation; the numbering in all other TSHβ gene mutations refers to the mature protein.
F, female; M, male; ND, not detected; Na, not available; T4, thyroxine; fT4, free thyroxine; Comp het, compound heterozygous.