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dc.contributor.author
Gutnisky, Viviana J.
dc.contributor.author
Moya, Christian M.
dc.contributor.author
Rivolta, Carina Marcela
dc.contributor.author
Domene, Sabina
dc.contributor.author
Varela, Viviana
dc.contributor.author
Toniolo, Jussara V.
dc.contributor.author
Medeiros Neto, Geraldo
dc.contributor.author
Targovnik, Hector Manuel
dc.date.available
2019-07-18T16:24:34Z
dc.date.issued
2004-02
dc.identifier.citation
Gutnisky, Viviana J.; Moya, Christian M.; Rivolta, Carina Marcela; Domene, Sabina; Varela, Viviana; et al.; Two Distinct Compound Heterozygous Constellations (R277X/IVS34-1G〉C and R277X/R1511X) in the Thyroglobulin (TG) Gene in Affected Individuals of a Brazilian Kindred with Congenital Goiter and Defective TG Synthesis; Endocrine Society; Journal of Clinical Endocrinology and Metabolism; 89; 2; 2-2004; 646-657
dc.identifier.issn
0021-972X
dc.identifier.uri
http://hdl.handle.net/11336/79797
dc.description.abstract
In this study, we have extended our initial molecular studies of a nonconsanguineous family with two affected siblings and one of their nephews with congenital goiter, hypothyroidism, and marked impairment of thyroglobulin synthesis. Genomic DNA sequencing revealed that the index patient (affected nephew) was heterozygous for a single base change of a cytosine to a thymine at nucleotide 886 in exon 7 (886C〉T, mother's mutation) in one allele and for a novel guanine to cytosine transversion at position-1 of the splice acceptor site in intron 34 (IVS34-1G〉C, father's mutation) in the other allele. The two affected siblings inherited the 886C〉T mutation from their mother and a previously reported cytosine to thymine transition at nucleotide 4588 in exon 22 from their father (4588C〉T). The 886C〉T and 4588C〉T substitutions resulted in premature stop codons at amino acids 277 (R277X) and 1511 (R1511X), respectively. In vitro transcription analysis showed that the exon 35 is skipped entirely when the IVS34-1G〉C mutation is present, whereas the wild-type allele is correctly spliced. SSCP (exon 7 and 35) and restriction analysis (exon 22) using Taq I indicated that the two affected siblings, the affected nephew, his mother, and his unaffected brother were all heterozygous for the R277X mutation. The two affected siblings, their father, and three unaffected siblings were all heterozygous for the R1511X mutation, whereas the affected nephew and his father were heterozygous for the IVS34-1G〉C mutation. Moreover, in this kindred, we have characterized polymorphisms (insertion/deletion, microsatellite, and single nucleotide polymorphism) located within introns 18 and 29 and exon 44 that are associated with the described mutations. Haplotype analysis with these polymorphic markers in two unrelated Brazilian families (present family studied and previously reported family) harboring the R277X mutation suggests a founder effect for the R277X mutation. In conclusion, the affected individuals of this family are either compound heterozygous for R277X/IVS34-1G〉C or R277X/R1511X. This observation further supports that thyroglobulin gene mutations display significant intraallelic heterogeneity.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Endocrine Society
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Hypothyroidism
dc.subject
Goitre
dc.subject
Thyroglobulin
dc.subject
Mutation
dc.subject.classification
Genética Humana
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Two Distinct Compound Heterozygous Constellations (R277X/IVS34-1G〉C and R277X/R1511X) in the Thyroglobulin (TG) Gene in Affected Individuals of a Brazilian Kindred with Congenital Goiter and Defective TG Synthesis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-07-16T14:13:59Z
dc.journal.volume
89
dc.journal.number
2
dc.journal.pagination
646-657
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Nueva York
dc.description.fil
Fil: Gutnisky, Viviana J.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.description.fil
Fil: Moya, Christian M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.description.fil
Fil: Rivolta, Carina Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.description.fil
Fil: Domene, Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.description.fil
Fil: Varela, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.description.fil
Fil: Toniolo, Jussara V.. Sao Paulo University School of Medicine; Brasil
dc.description.fil
Fil: Medeiros Neto, Geraldo. Sao Paulo University School of Medicine; Brasil
dc.description.fil
Fil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.journal.title
Journal of Clinical Endocrinology and Metabolism
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/14764776
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1210/jc.2003-030587
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jcem/article/89/2/646/2840770


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