Complicated Relationship between Genetic Mutations and Phenotypic Characteristics in Transient and Permanent Congenital Hypothyroidism: Analysis of Pooled Literature Data
Table 1
Characteristics comparison between the TCH and PCH cases.
Chi-square test
Univariate analysisf
TCH (n = 94)
PCH (n = 147)
Total (n = 241)
OR
95% CI
Continent
<0.001
Africa
0 (0.00%)
1 (0.68%)
1
Reference
Asia
85 (90.43%)
90 (61.22%)
175
§
Europea
5 (5.32%)
50 (34.01%)
55
§
South America
4 (4.26%)
6 (4.08%)
10
§
Sex
0.958
Male
48 (52.17%)
62 (52.54%)
110
Reference
Female
44 (47.83%)
56 (47.46%)
100
0.99
0.57–1.70
0.958
Unknownb
2
29
31
NA
Thyroid morphology
<0.001
Normal
30 (34.48%)
37 (28.46%)
67
Reference
Goiter/enlarged
56 (64.37%)
67 (51.54%)
123
0.97
0.53–1.76
0.921
Small volume/ectopy
1 (1.15%)
26 (20.00%)
27
21.08
2.70–164.37
0.004
Unknownb
7
17
24
NA
Gene classificationc
<0.001
Gene relating to TDH
93 (98.94%)
102 (69.39%)
195
Reference
Gene relating to TD
1 (1.06%)
41 (27.89%)
42
37.38
5.04–277.21
<0.001
Gene relating to TDH and TD
0 (0.00%)
4 (2.72%)
4
§
Type of mutationd
0.028
Single missense mutation
18 (19.15%)
53 (36.05%)
71
Reference
Single non-missense mutation
34 (36.17%)
41 (27.89%)
75
0.41
0.20–0.83
0.013
Dual-site mutations
34 (36.17%)
47 (31.97%)
81
0.47
0.23–0.94
0.033
Multisite mutations
8 (8.51%)
6 (4.08%)
14
0.25
0.08–0.83
0.024
Mutation statee
0.419
Heterozygous
44 (46.81%)
74 (50.34%)
118
Reference
Homozygous
8 (8.51%)
20 (13.61%)
28
1.49
0.60–3.66
0.388
Compound heterozygous
40 (42.55%)
49 (33.33%)
89
0.73
0.42–1.28
0.267
Combinational heterozygous
2 (2.13%)
4 (2.72%)
6
1.19
0.21–6.76
0.845
Mutation location
0.143
Monoallelic
44 (46.81%)
83 (56.46%)
127
Reference
Biallelic
50 (53.19%)
64 (43.54%)
114
0.68
0.40–1.14
0.144
aOne French-Canadian case with TCH was included in the Europe group. bCases with unknown sex or thyroid morphology were not included in the comparison of TCH vs. PCH. cGene classification was based on the function of the gene according to previous studies. The TDH genes included DUOX2, DUOXA2, TG, and TPO; the TD genes included FOXE1, NKX2-5, PAX8, and TSHR; and the TDH and TD genes included DUOX2 and TSHR. dSingle non-missense mutations, including single nonsense, frameshift, splice site, or in-frame mutations. One TCH case with a 43 kB pair deletion of chromosome 15 (encompassing DUOX2, DUOXA1, and DUOXA2) was included in the group of multisite mutations. eCompound heterozygous cases harbored at least two mutations of one gene. Combinational heterozygous cases harbored mutations of two different genes. fThe odds ratio refers to TCH vs. PCH. §The analysis failed because of the small sample size. TCH: transient congenital hypothyroidism; PCH: permanent congenital hypothyroidism; TDH: thyroid dyshormonogenesis; TD: thyroid dysgenesis; NA: not analyzed.
