A new compound heterozygous for c.886C>T/c.2206C>T [p.R277X/p.Q717X] mutations in the thyroglobulin gene as a cause of foetal goitrous hypothyroidism

CINTIA E. CITTERIO; REGIS COUNTANT; STEPHANIE ROULEAU; JOSÉ M. MIRALLES-GARCÍA; ROGELIO GONZÁLEZ-SARMIENTO; CARINA M. RIVOLTA; HÉCTOR M. TARGOVNIK

CLINICAL ENDOCRINOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Oxford; Año: 2011 vol. 74 p. 533 - 535

0300-0664

The identification of thyroglobulin (TG) mutations has contributed significantly to the understanding of the molecular pathogenesis of congenital hypothyroidism because of dyshormonogenesis, an autosomal recessive inherited disorder characterized by congenital goitre. Fifty-one germline mutations have been identified in the human TG. Although the incidence of TG mutations is still unknown in France, previous studies have reported four TG mutations in two compound heterozygous patients.2,3 In the first, a foetal goitrous hypothyroidism, the paternal mutation consisted of a cytosine deletion at nucleotide 1143 in exon 9 (c.1143delC), resulting in a frameshift which generated a stop codon at position 382(p.G362fsX382), and the maternal mutation was a c.6725G>A in exon 38, creating the p.R2223H missense mutation in the acetylcholinesterase (ACHE)-homology domain of the TG.3 The second patient was heterozygous for a nonsense mutation because of a c.4588C>T at exon 22 [p.R1511X] (father´s mutation) and for a c.5386C>T at exon 27 [p.Q1777X] (mother´s mutation). The aim of the present study was to characterize a novel compound heterozygous for TG mutations in a French family with foetal goitrous hypothyroidism.