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

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RESEARCH PRODUCT

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

Norma Leonard Pia Hermanns Robert Couch Cherise Klotz Joachim Pohlenz

subject

Male Thyrotropin-beta Untranslated region endocrine system medicine.medical_specialty Turkey endocrine system diseases Endocrinology Diabetes and Metabolism Thyrotropin Thyrotropin beta Subunit Biology Polymerase Chain Reaction Exon Endocrinology Hypothyroidism Internal medicine medicine Central hypothyroidism Humans Gene Oligonucleotide Array Sequence Analysis Genetics Infant Nucleic Acid Hybridization DNA Jaundice medicine.disease Congenital hypothyroidism Thyroxine Endocrinology Pediatrics Perinatology and Child Health medicine.symptom Gene Deletion Comparative genomic hybridization

description

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.

year	journal	country	edition	language
2014-01-13	Hormone Research in Paediatrics

https://doi.org/10.1159/000362413