A Novel Deletion in the Thyrotropin Beta-Subunit Gene Identified by Array Comparative Genomic Hybridization Analysis Causes Central Congenital Hypothyroidism in a Boy Originating from Turkey

作者：Hermanns Pia; Couch Robert; Leonard Norma; Klotz Cherise; Pohlenz Joachim^*

来源：Hormone Research in Paediatrics, 2014, 82(3): 201-205.

DOI：10.1159/000362413

• Central hypothyroidism
• Array comparative genomic hybridization analysis
• Thyrotropin deficiency

Background: Isolated central congenital hypothyroidism (ICCH) is rare but important. Most ICCH patients are diagnosed later, which results in severe growth failure and intellectual disability. Objective: We describe a boy with ICCH due to a large homozygous TSH beta gene deletion. Results: A 51-day-old male Turkish infant, whose parents were first cousins, was admitted for evaluation of prolonged jaundice. His clinical appearance was compatible with hypothyroidism. Venous thyrotropin (TSH) was undetectably low, with a subsequent low free T4 and a low free T3, suggestive of central hypothyroidism. Using different PCR protocols, we could not amplify both coding exons of the boy's TSH beta gene, which suggested a deletion. An array comparative genomic hybridization (aCGH) using specific probes around the TSH beta gene locus showed him to be homozygous for a 6-kb deletion spanning all exons and parts of the 5' untranslated region of the gene. Conclusions: Infants who are clinically suspected of having hypothyroidism should be evaluated thoroughly, even if their TSH-based screening result is normal. In cases with ICCH and undetectably low TSH serum concentrations, a TSH beta gene deletion should be considered; aCGH should be performed when gene deletions are suspected. In such cases, PCR-based sequencing techniques give negative results.

• 出版日期2014