IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Novel mutational mechanism in the thyroglobulin gene: Imperfect DNA inversion as a cause for hereditary hypothyroidism.
Autor/es:
CITTERIO CINTIA E; ROSSETTI LILIANA C; SOUCHON PIERRE F; CECILIA MORALES; MATHILDE THOUVARD-VIPREY; ANNE S. SALMON-MUSIAL; PIERRE L.A. MAURAN; MARTINE DOCO-FENZY; ROGELIO GONZÁLEZ-SARMIENTO; CARINA M. RIVOLTA; CARLOS D. DE BRASI; TARGOVNIK, HECTOR M.
Revista:
MOLECULAR AND CELLULAR ENDOCRINOLOGY.
Editorial:
ELSEVIER IRELAND LTD
Referencias:
Lugar: Amsterdam; Año: 2013 vol. 381 p. 220 - 229
ISSN:
0303-7207
Resumen:
The objective of this study was to perform
genetic analysis in three brothers of Turkish origin born from consanguineus
parents and affected by congenital hypothyroidism, goiter and low levels of
serum TG. The combination of sequencing of DNA, PCR mapping, quantitative
real-time PCR, inverse-PCR (I-PCR), multiplex PCR and bioinformatics analysis
were used in order to detect TG mutations. We demonstrated that the three
affected siblings are homozygous for a DNA inversion of 16,962 bp in the TG
gene associated with two deleted regions at both sides of the inversion limits.
The inversion region includes the first 9 bp of exon 48, 1015 bp of intron 47,
191 bp of exon 47, 1523 bp of intron 46, 135 bp of exon 46 and the last 14,089
bp of intron 45. The proximal deletion corresponds to 27 bp of TG intron 45, while
the distal deletion spans the last 230 bp of TG exon 48 and the first 588 bp of
intergenic region downstream TG end. The parents were heterozygous carriers of
the complex rearrangement. In conclusion, a novel large imperfect DNA inversion
within the TG gene was identified by the strategy of I-PCR. This aberration was
not detectable by normal sequencing of the exons and exon/intron boundaries. Remarkably,
the finding represents the first description of a TG deficiency disease caused
by a DNA inversion.