Original Paper

Screening for Pax8 Mutations in Patients with Congenital Hypothyroidism in South-West Germany
Kirsten Lanzerath^a, Markus Bettendorf^a, Christine Haag^b, Caroline Kneppo^a, Egbert Schulze^b, Jürgen Grulich-Henn<sup>a

a</sup>Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics, University of Heidelberg, and
^bLaboratory for Molecular Genetics, Endocrine Practice, Heidelberg, Germany

Address of Corresponding Author

Horm Res 2006;66:96-100 (DOI: 10.1159/000093799)

  Key Words

• Congenital hypothyroidism
• Pax8 gene mutations
• Germany, incidence

  Abstract

Aims: To study the frequency of mutations in the Pax8 gene in a cohort of patients with congenital hypothyroidism (CH) in South West Germany. Methods: A cohort of 95 patients with CH (60 females, 35 males), identified in our newborn screening program, was analyzed for mutations in Pax8 by single-stranded conformational polymorphism (SSCP) and DNA sequencing. Results: SSCP analysis and direct sequencing of exon 3 of a female patient with a hypoplastic thyroid gland revealed two heterozygous mutations in Pax8 resulting in a transition of T to C (codon 34) and G to A (codon 35), replacing isoleucine by threonine and valine by isoleucine. Using allele-specific PCR we could demonstrate that both mutations are located on the same allele. Furthermore, a polymorphism was documented in 24 patients with thyroid hypoplasia in intron 6 at nucleotide +51 (CC, GG, CG). Comparison of the polymorphisms between hypothyroid patients and controls revealed no significant differences suggesting that this polymorphism does not play a role in the pathogenesis of hypothyroidism. No further mutations or polymorphisms were found in the cohort. Conclusions: These findings confirm the contribution of mutations in the Pax8 gene to the etiology of thyroid dysgenesis with a variable penetrance, but also demonstrate the rare overall incidence in CH.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Dr. Jürgen Grulich-Henn, Sektion Pädiatrische Endokrinologie und Diabetologie Universitätsklinik für Kinder und Jugendmedizin, Im Neuenheimer Feld 150
DE-9120 Heidelberg (Germany)
Tel. +49 6221 568 399, Fax +49 6221 564 126
E-Mail Juergen_Grulich-Henn@med.uni-heidelberg.de

  Article Information

Received: June 24, 2005
Accepted: April 21, 2006
Published online: June 7, 2006
Number of Print Pages : 5
Number of Figures : 2, Number of Tables : 2, Number of References : 19