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Titolo:
CONGENITAL HYPOTHYROIDISM DUE TO MUTATIONS IN THE SODIUM IODIDE SYMPORTER - IDENTIFICATION OF A NONSENSE MUTATION PRODUCING A DOWNSTREAM CRYPTIC 3'-SPLICE-SITE/
Autore:
POHLENZ J; ROSENTHAL IM; WEISS RE; JHIANG SM; BURANT C; REFETOFF S;
Indirizzi:
UNIV CHICAGO,DEPT MED,5841 S MARYLAND AVE CHICAGO IL 60637 UNIV CHICAGO,DEPT MED CHICAGO IL 60637 UNIV CHICAGO,DEPT PEDIAT CHICAGO IL 60637 UNIV CHICAGO,JOSEPH P KENNEDY JR MENTAL RETARDAT RES CTR CHICAGO IL 60637 OHIO STATE UNIV,DEPT INTERNAL MED COLUMBUS OH 43210 OHIO STATE UNIV,DEPT PHYSIOL COLUMBUS OH 43210
Titolo Testata:
The Journal of clinical investigation
fascicolo: 5, volume: 101, anno: 1998,
pagine: 1028 - 1035
SICI:
0021-9738(1998)101:5<1028:CHDTMI>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
SODIUM-IODIDE SYMPORTER; COTRANSPORTER SGLT1; THYROID-HORMONE; EXON MUTATION; BETA-GENE; EXPRESSION; RESISTANCE; FAMILIES; CLONING; DEFECTS;
Keywords:
FRAMESHIFT; GENETICS; THYROID; IODIDE TRANSPORT; ALLELE-SPECIFIC AMPLIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
J. Pohlenz et al., "CONGENITAL HYPOTHYROIDISM DUE TO MUTATIONS IN THE SODIUM IODIDE SYMPORTER - IDENTIFICATION OF A NONSENSE MUTATION PRODUCING A DOWNSTREAM CRYPTIC 3'-SPLICE-SITE/", The Journal of clinical investigation, 101(5), 1998, pp. 1028-1035

Abstract

A 12-yr-old hypothyroid girl was diagnosed at birth as athyreotic because her thyroid gland could not be visualized by isotope scanning. Goiter development due to incomplete thyrotropin suppression, a thyroidal radioiodide uptake of < 1%, and a low saliva to plasma ratio of 2.5 suggested iodide (I-) transport defect, mRNA isolated from her thyroidgland and injected into Xenopus oocytes failed to increase I- transport. Sequencing of the entire Na+/I- symporter (NIS) cDNA revealed a C to G transversion of nucleotide (nt) 1146 in exon 6, resulting in a Gln 267 (CAG) to Glu (GAG) substitution, This missense mutation producesan NIS with undetectable I- transport activity when expressed in COS-7 cells, Although only this missense mutation was identified in thyroid and lymphocyte cDNA, genotyping revealed that the proposita and her unaffected brother and father were heterozygous for this mutation. However, amplification of cDNA with a primer specific for the wild-type nt 1146 yielded a sequence lacking 67 nt. Genomic DNA showed a C to G transversion of nt 1940 producing a stop codon as well as a new downstream cryptic 3' splice acceptor site in exon 13, responsible far the 67nt deletion, frameshift, and premature stop predicting an NIS lacking129 carboxy-terminal amino acids, This mutation was inherited from the mother and present in the unaffected sister. Thus, although the proposita is a compound heterozygote, because of the very low expression (< 2.5%) of one mutant allele, she is functionally hemizygous for an NIS without detectable bioactivity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 09:15:48