ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume : 7 Issue : 3 Year : 2024
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Turkish Society for Pediatric Endocrinology and Diabetes
The Missense Alteration A5T of the Thyroid Peroxidase Gene is Pathogenic and Associated with Mild Congenital Hypothyroidism [J Clin Res Pediatr Endocrinol]
J Clin Res Pediatr Endocrinol. 2015; 7(3): 238-241 | DOI: 10.4274/jcrpe.2017

The Missense Alteration A5T of the Thyroid Peroxidase Gene is Pathogenic and Associated with Mild Congenital Hypothyroidism

Hakan Cangül1, Korcan Demir2, Korcan Demir2, H. Ömür Babayiğit3, Ayhan Abacı4, Ece Böber2
1Medipol University Faculty Of Medicine, Department Of Medical Genetics, İstanbul, Turkey
2Dokuz Eylül University Faculty Of Medicine, Department Of Pediatric Endocrinology, İzmir, Turkey
3Dokuz Eylül University Faculty Of Medicine, Department Of Pediatrics, İzmir, Turkey
4Dokuz Eylül University Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey

Congenital hypothyroidism (CH) occurs with a prevalence of approximately 1:4000 live births. Defects of thyroid hormone synthesis account for 15-20% of these cases. Thyroid peroxidase (TPO) gene is the most common cause for dyshormonogenesis. So far, more than 60 mutations in the TPO gene have been described, resulting in a variable decrease in TPO bioactivity. We present an 8-day-old male with mild CH who was identified to have a G to A transition in the fifth codon of the TPO gene (c.13G>A; p.Ala5Thr). The unaffected family members were heterozygous carriers of the mutation, whereas 400 healthy individuals of the same ethnic background did not have the mutation. Mutation analysis of 11 known causative CH genes and 4 of our own strong candidate genes with next-generation sequencing revealed no mutations in the patient nor in any other family members. The results of in silico functional analyses indicated partial loss-of-function (LOF) in the resulting enzyme molecule due to mutation. The patient’s clinical finding s were consistent with the effect of this partial LOF of the mutation. In conclusion, we strongly believe that A5T alteration in the TPO gene is actually pathogenic and suggest that it should be classified as a mutation.

Keywords: congenital hypothyroidism,thyroid dyshormonogenesis,thyroid peroxidase

Hakan Cangül, Korcan Demir, Korcan Demir, H. Ömür Babayiğit, Ayhan Abacı, Ece Böber. The Missense Alteration A5T of the Thyroid Peroxidase Gene is Pathogenic and Associated with Mild Congenital Hypothyroidism. J Clin Res Pediatr Endocrinol. 2015; 7(3): 238-241
Manuscript Language: English
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