INVESTIGADORES
PELLIZAS Claudia Gabriela
artículos
Título:
Congenital Hypothyroidism with Goiter Caused by New Mutations in the Thyroglobulin Gene
Autor/es:
CAPUTTO M; RIVOLTA C; ESPERANTE S; GRUÑEIRO-PAPENDIECK L; CHIESA A; PELLIZAS CG; GONZÀLEZ SARMIENTO R; TARGOVNIK HM
Revista:
CLINICAL ENDOCRINOLOGY
Editorial:
Society for Endocrinology
Referencias:
Año: 2007 vol. 67 p. 351 - 357
ISSN:
0300-0664
Resumen:
C o n te x t Thyroid dyshormonogenesis is associated with mutations
in the thyroglobulin (TG) gene and characterized by normal organifi-
cation of iodide and low serum TG. These mutations give rise to
congenital goitrous hypothyroidism, transmitted in an autosomal
recessive mode.
O b j e c ti v e s The aim of this study was to identify new mutations
in the TG gene in an attempt to increase the understanding of the
molecular basis of this disorder. Three unrelated patients with
marked impairment of TG synthesis were studied.
Met h o d s The promoter and the complete coding regions of the TG
gene, along with the flanking intronic regions, were analysed by
direct DNA sequencing.
Res u l t s Four different inactivating TG mutations, three novel
mutations (c.548G>A, p.C164Y; c.759760insA, p.L234fsX237;
c.6701C>A, p.A2215D) and one previously identified mutation
(c.886C>T, p.R277X) were identified. Multiple sequence alignment
study revealed that the wild-type cysteine residue at position 164 is
strictly conserved in the TG of all the species analysed, whereas the
wild-type alanine residue at position 2215 is well conserved in the
TG and acetylcholinesterase (AChE) of all the species analysed except
in rabbit AChE, in which it is substituted by glutamic acid.
C on c l u s i o n s We report three patients with congenital hypothyroidism with goitre caused by two compound heterozygous
mutations, p.C164Y/p.L234fsX237 and p.R277X/p.A2215D, and one
homozygous mutation, p.R277X, in the TG gene. To our knowledge
this is the first report of the presence of a nucleotide insertion
mutation in the TG gene.