Screening for Pax8 mutations in patients with congenital hypothyroidism in South-West Germany.
OBJECTIVE
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.
Lanzerath
Kirsten
K
Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.
Bettendorf
Markus
M
Haag
Christine
C
Kneppo
Caroline
C
Schulze
Egbert
E
Grulich-Henn
Jürgen
J
D000328:Adult; D015331:Cohort Studies; D003409:Congenital Hypothyroidism / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005860:Germany, West; D006801:Humans; D007231:Infant, Newborn; D007438:Introns; D008297:Male; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011110:Polymorphism, Genetic
D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors