RSS-Feed abonnieren
DOI: 10.1055/s-0033-1333766
Congenital Goitrous Primary Hypothyroidism in Two German Families Caused by Novel Thyroid Peroxidase (TPO) Gene Mutations
Publikationsverlauf
received 26. November 2012
first decision 14. Januar 2013
accepted 22. Januar 2013
Publikationsdatum:
19. März 2013 (online)
![](https://www.thieme-connect.de/media/eced/201306/lookinside/thumbnails/10.1055-s-0033-1333766-1.jpg)
Abstract
Congenital hypothyroidism occurs with a prevalence of approximately 1:3 500. Defects in thyroid hormone synthesis which lead to goitrous hypothyroidism account for 10–15% of these cases. Several genetic defects have been characterized and mutations in the thyroid peroxidase (TPO) gene are the most common cause for dyshormonogenesis.
So far, more than 80 mutations in the TPO gene have been described, resulting in a variable decrease in TPO bioactivity. Clinically TPO defects manifest with congenital primary goitrous hypothyroidism.
We here present 2 children with congenital primary hypothyroidism, who were identified to have compound heterozygous TPO mutations. They both shared the same novel mutation in the TPO gene (C756R) in exon 13. One case presented with an apparently dominant inheritance of thyroid dyshormonogenesis.
-
References
- 1 Deladoey J, Belanger N, Van Vliet G. Random variability in congenital hypothyroidism from thyroid dysgenesis over 16 years in Quebec. J Clin Endocrinol Metab 2007; 92: 3158-3161
- 2 Van Vliet G. Hypothyroidism in infants and children. In: Braverman LE. ed. The thyroid: a fundamental and clinical text. 9th ed. New York: Lippincott; 2005: 1029-1047
- 3 Avbelj M, Tahirovic H, Debeljak M et al. High prevalence of thyroid peroxidase gene mutations in patients with thyroid dyshormonogenesis. Eur J Endocrinol 2007; 156: 511-519
- 4 Medeiros-Neto G, Stanbury JB. Inherited disorders of the thyroid system. Boca Raton, FL: CRC Press, Inc; 1994
- 5 Ohtaki S, Nakagawa H, Nakamura M et al. Thyroid peroxidase: experimental and clinical integration. Endocr J 1996; 43: 1-14
- 6 Endo Y, Onogi S, Umeki K et al. Regional localization of the gene for thyroid peroxidase to human chromosome 2p25 and mouse chromosome 12C. Genomics 1995; 25: 760-761
- 7 Kimura S, Hong YS, Kotani T et al. Structure of the human thyroid peroxidase gene: comparison and relationship to the human myeloperoxidase gene. Biochemistry 1989; 28: 4481-4489
- 8 Pannain S, Weiss RE, Jackson CE et al. Two different mutations in the thyroid peroxidase gene of a large inbred Amish kindred: power and limits of homozygosity mapping. J Clin Endocrinol Metab 1999; 84: 1061-1071
- 9 Fugazzola L, Mannavola D, Vigone MC et al. Total iodide organification defect: clinical and molecular characterization of an Italian family. Thyroid 2005; 15: 1085-1088
- 10 Calaciura F, Miscio G, Coco A et al. Genetics of specific phenotypes of congenital hypothyroidism: a population-based approach. Thyroid 2002; 12: 945-951
- 11 Bakker B, Bikker H, Vulsma T et al. Two decades of screening for congenital hypothyroidism in The Netherlands: TPO gene mutations in total iodide organification defects (an update). J Clin Endocrinol Metab 2000; 85: 3708-3712
- 12 Nascimento AC, Guedes DR, Santos CS et al. Thyroperoxidase gene mutations in congenital goitrous hypothyroidism with total and partial iodide organification defect. Thyroid 2003; 13: 1145-1151
- 13 Abramowicz MJ, Targovnik HM, Varela V et al. Identification of a mutation in the coding sequence of the human thyroid peroxidase gene causing congenital goiter. J Clin Invest 1992; 90: 1200-1204
- 14 Rivolta CM, Esperante SA, Gruneiro-Papendieck L et al. Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect. Hum Mutat 2003; 22: 259
- 15 Santos CL, Bikker H, Rego KG et al. A novel mutation in the TPO gene in goitrous hypothyroid patients with iodide organification defect. Clin Endocrinol (Oxf) 1999; 51: 165-172
- 16 Rodrigues C, Jorge P, Soares JP et al. Mutation screening of the thyroid peroxidase gene in a cohort of 55 Portuguese patients with congenital hypothyroidism. Eur J Endocrinol 2005; 152: 193-198
- 17 Gruters A, Kohler B, Wolf A et al. Screening for mutations of the human thyroid peroxidase gene in patients with congenital hypothyroidism. Exp Clin Endocrinol Diabetes 1996; 104 (Suppl. 04) 121-123
- 18 Deladoey J, Pfarr N, Vuissoz JM et al. Pseudodominant inheritance of goitrous congenital hypothyroidism caused by TPO mutations: molecular and in silico studies. J Clin Endocrinol Metab 2008; 93: 627-633
- 19 Adzhubei IA, Schmidt S, Peshkin L et al. A method and server for predicting damaging missense mutations. Nat Methods 2010; 7: 248-249
- 20 Pfarr N, Borck G, Turk A et al. Goitrous congenital hypothyroidism and hearing impairment associated with mutations in the TPO and SLC26A4/PDS genes. J Clin Endocrinol Metab 2006; 91: 2678-2681
- 21 Borgel K, Pohlenz J, Holzgreve W et al. Intrauterine therapy of goitrous hypothyroidism in a boy with a new compound heterozygous mutation (Y453D and C800R) in the thyroid peroxidase gene. A long-term follow-up. Am J Obstet Gynecol 2005; 193: 857-858