Ann Pediatr Endocrinol Metab.  2019 Sep;24(3):199-202. 10.6065/apem.2019.24.3.199.

Congenital hypothyroidism due to thyroglobulin deficiency: a case report with a novel mutation in TG gene

• Heo S
• Jang JH
• Yu J

• KMID: 2460768
• DOI: http://doi.org/10.6065/apem.2019.24.3.199

Abstract

Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates and infants with an incidence of one in 2,000 to one in 4,000 newborns. Primary CH can be caused by thyroid dysgenesis and thyroid dyshormonogenesis. CH due to a TG gene mutation is one cause of thyroid dyshormonogenesis and can be characterized by goitrous CH with absent or low levels of serum thyroglobulin (Tg). In the present case, a 15-day-old neonate was referred to us with elevated thyroid stimulating hormone detected during a neonatal screening test. At the age of 34 months, extensive genetic testing was performed, including targeted exome sequencing for hypothyroidism, and revealed compound heterozygous mutations in the TG gene. Sanger sequencing of both parents' DNA samples revealed a c.3790T> C (p.Cys1264Arg) mutation located at exon 17 inherited from the mother, and a c.4057C> T (p.Gln1353*) mutation located at exon 19 was inherited from the father. The c.4057C> T (p.Gln1353*) mutation located at exon 19 has never been reported and, therefore, is a new discovery. We report a case of primary permanent CH with compound heterozygous mutations of the TG gene, including a novel mutation.

Keyword

Congenital hypothyroidism; Novel mutation; Thyroglobulin

MeSH Terms

Congenital Hypothyroidism*
DNA
Exome
Exons
Fathers
Genetic Testing
Humans
Hypothyroidism
Incidence
Infant
Infant, Newborn
Mothers
Neonatal Screening
Thyroglobulin*
Thyroid Dysgenesis
Thyroid Gland
Thyrotropin
DNA
Thyroglobulin
Thyrotropin

Figure

• 

  Fig. 1. Laboratory findings and levothyroxine dose. Initially, an elevated TSH (>100.0 uIU/mL), decreased T3 (73.17 ng/dL), and fT4 (0.228 ng/mL) were noted, and the Tg level was 5.53 ng/mL. During the treatment with levothyroxine, a euthyroid state was maintained, but the Tg (red dots) remained low. Left axis: Levothyroxine, Tg, and fT4. Right axis: T3 and TSH. Tg, thyroglobulin; fT4, free T4; T3, total T3; TSH, thyroid stimulating hormone.

• 

  Fig. 2. Results of Sanger sequencing of TG gene. (A) c.3790T>C (p.C1264R) was located at exon 17. It is a known mutation affecting the intracellular transport of thyroglobulin. (B) c.4057C>T (p.Q1353*) was located at exon 19, and this is a novel mutation in which the 1353th amino acid glutamine is replaced with a stop codon. P, Proband; F, Father; M, Mother.

Reference

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