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.

Abstract

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 TSHβ 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 TSHβ gene, which suggested a deletion. An array comparative genomic hybridization (aCGH) using specific probes around the TSHβ 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 TSHβ gene deletion should be considered; aCGH should be performed when gene deletions are suspected. In such cases, PCR-based sequencing techniques give negative results.

• Authors: Pia Hermanns, Robert Couch, Norma Leonard, Cherise Klotz, Joachim Pohlenz
• Journal: Hormone research in paediatrics (Horm Res Paediatr) Vol. 82 Issue 3 Pg. 201-5 ( 2014) ISSN: 1663-2826 [Electronic] Switzerland
• PMID: 25012771 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Thyrotropin, beta Subunit
• Thyrotropin
• DNA
• Thyroxine

Topics

• DNA (genetics)
• Gene Deletion
• Humans
• Hypothyroidism (genetics)
• Infant
• Male
• Nucleic Acid Hybridization
• Oligonucleotide Array Sequence Analysis
• Polymerase Chain Reaction
• Thyrotropin (blood)
• Thyrotropin, beta Subunit (genetics)
• Thyroxine (blood)
• Turkey