A RECURRENT MUTATION IN TSHB GENE UNDERLYING CENTRAL CONGENITAL HYPOTHYROIDISM UNDETECTABLE IN NEONATAL SCREENING

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Central congenital hypothyroidism (CCH) is a rare endocrine disorder affecting thyroid hormone production.
• Isolated CCH, specifically TSH deficiency, can be challenging to detect through standard neonatal screening methods.

Observation:

• A case report details a 5-month-old boy with a delayed diagnosis of isolated CCH.
• Molecular analysis revealed a recurrent TSHB gene mutation (c.373delT) in the patient, with parents and sister identified as carriers.

Findings:

• The c.373delT mutation in the TSHB gene is a recurring cause of isolated TSH deficiency, identified across multiple international populations.
• This specific mutation has been previously documented in diverse geographical regions, suggesting a potential commonality.

Implications:

• The findings underscore the importance of molecular genetic studies for diagnosing isolated TSH deficiency, especially when neonatal screening is inconclusive.
• Identifying affected individuals and carriers through genetic analysis facilitates timely diagnosis, treatment, and essential genetic counseling.