Genotype–Phenotype Correlations in 30 Japanese Patients With Congenital Hypothyroidism Attributable to TG Defects
Authors' conclusion
To our knowledge, this is the largest investigation on the clinical presentation of TG defects diagnosed in the neonatal period. Patients with missense variants showed relatively mild hypothyroidism with compensative goiter. Patients with only truncating variants showed minimal or no compensative goiter and required full hormone replacement.
Study context
- Population
- Japanese patients with congenital hypothyroidism attributable to TG defects, identified by screening 1061 patients with congenital hypothyroidism (CH) for 13 CH-related genes; all but one diagnosed via newborn screeningof 1061 screened
- Participants
- 30 patients
- Exposure
- Biallelic truncating vs monoallelic/biallelic missense TG variants
- Biallelic truncatingn = 13
- Missensen = 17
- Outcome
- Clinical characteristics by genotype
Methodological detailsgenotype–phenotype comparison, HEK293 cell functional assays
- Genotype–phenotype comparison
- HEK293 cell functional assays
Main finding
As reported in the abstract
- Thyroid enlargement with TSH stimulation more likely with missense than biallelic truncating variants
- Biallelic truncating variants invariably required full hormone replacement; missense variants required variable LT4 doses
Observational data: associations, not effects.
Further findings
Rare TG variants detected
- Rare TG variants
- 27
- Nonsense
- 15
- Frameshift
- 3
- Splice-site
- 2
- Missense
- 7
In vitro function of missense variants
- Loss of function of the 7 missense variants confirmed in vitro
Original publication
Genotype–Phenotype Correlations in 30 Japanese Patients With Congenital Hypothyroidism Attributable to TG Defects. J Clin Endocrinol Metab. Published 19 February 2024. doi:10.
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