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Pathogenic variants in the thyrotropin receptor gene (TSHR) have been implicated in a subset of congenital hypothyroidism due to athyreosis. In a cohort of 100 Chinese patients with congenital hypothyroidism and athyreosis, seven unrelated probands harbored heterozygous missense TSHR variants, including c.491T>A (p.Met164Lys) (7 probands ([PMID:28455095])). All identified changes were missense substitutions without accompanying family segregation data. No functional assays were performed to validate these variants in the context of thyroid dysgenesis. Consequently, the current association is supported solely by variant discovery in affected individuals. Overall, evidence for a causative role of TSHR in athyreosis remains limited.
Key take-home: TSHR sequencing can identify rare missense variants in a small fraction of congenital athyreosis cases, aiding molecular diagnosis.
Gene–Disease AssociationLimited7 probands with TSHR variants in congenital hypothyroidism and athyreosis ([PMID:28455095]); no segregation or disease-specific functional validation Genetic EvidenceLimited7 missense variants identified in unrelated probands ([PMID:28455095]); absence of familial segregation Functional EvidenceNot applicableNo functional studies of TSHR variants in athyreosis; existing assays pertain to other thyroid phenotypes |