Molecular and Clinical Features of Congenital Hypothyroidism Due to Multiple DUOX2 Variants
Authors' conclusion
These results broaden the mutational spectrum of DUOX2. Furthermore, our data imply that patients with multiple pathogenic DUOX2 variants typically exhibit transient CH without significant genotype-phenotype correlations. Most importantly, this study demonstrated for the first time that these patients are at risk of developing recurrent hypothyroidism after a long drug-free interval.
Study context
- Population
- Patients with congenital hypothyroidism (CH) screened for rare variants of 11 known causative genes; clinical analyses in patients with multiple pathogenic DUOX2 variants but not of other genes
- Participants
- 255 patients
- Outcome
- DUOX2 variants identified
Methodological detailsin vitro functional assays, long-read amplicon sequencing, haplotype phasing
- In vitro functional assays
- Long-read amplicon sequencing
- Haplotype phasing
Main finding
As reported in the abstract
- Pathogenic DUOX2 variants identified, in 63 patients
- 24
- Benign variants
- 2
- Variants of uncertain significance
- 7
- Novel pathogenic variants not yet linked to CH (3 missense, 1 frameshift)
- 4
- Patients with multiple pathogenic DUOX2 variants without other pathogenic gene variants
- 21
- Of the 21, homozygous variants
- 3
- Of the 21, compound heterozygosity confirmed
- 14
- Of the 21, allelic positions undetermined
- 4
Observational data: associations, not effects.
Further findings
Clinical course in the 21 patients with multiple pathogenic DUOX2 variants
- Treated with LT4
- 19
- Age at drug withdrawal
- 9 months to 21.4 years
- Required retreatment after drug-free intervals of 6 months, 8 months and 10 years
- 3
- No differences in clinical severity among amorphic/amorphic, amorphic/hypomorphic and hypomorphic/hypomorphic genotypes
Original publication
Molecular and Clinical Features of Congenital Hypothyroidism Due to Multiple DUOX2 Variants. Thyroid. Published 7 June 2024. doi:10.
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