Digenic Inheritance Mode in Congenital Hypothyroidism Due to Thyroid Dysgenesis: HYPOTYGEN Translational Cohort Study
Authors' conclusion
This work expands our understanding of the molecular causes of CHTD by demonstrating that digenic inheritance can be implicated, with deleterious variants in thyroid development and DUOX2/DUOXA2 genes. The complexity of this model implies a revision of the genetic landscape of CHTD and specific clinical care of patients during long-term follow-up.
Study context
- Population
- Patients with congenital hypothyroidism (CH) diagnosed through systematic newborn screening in France (HYPOTYGEN cohort); focus on thyroid dysgenesis (CHTD)292 genetically analysed
- Participants
- 514 patients
- Outcome
- Inheritance mode of CHTD
Methodological detailsmulticenter, nationwide, translational, targeted next-generation sequencing (78-gene panel), familial segregation, in vitro functional studies
- Multicenter
- Nationwide
- Translational
- Targeted next-generation sequencing (78-gene panel)
- Familial segregation
- In vitro functional studies
Main finding
As reported in the abstract
Disease-causing mutation in 1 of the 10 known CHTD genes
20 of 292
6.8%
Digenic inheritance: variant in a thyroid development gene plus a variant in DUOX2/DUOXA2
16
5.5%
Observational data: associations, not effects.
Further findings
Malformations (clinical phenotypes of 458 patients)
- Cardiac malformations
- 7.7% (14/182)
- Renal malformations
- 3.9% (7/178)
Original publication
Digenic Inheritance Mode in Congenital Hypothyroidism Due to Thyroid Dysgenesis: HYPOTYGEN Translational Cohort Study. J Clin Endocrinol Metab. Published 9 January 2025. doi:10.
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