New splicing mutation of <i>MEN1</i> gene affecting the translocation of menin to the nucleous

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dc.contributor.authorTala, H. P.
dc.contributor.authorCarvajal, C. A.
dc.contributor.authorGonzalez, A. A.
dc.contributor.authorGarrido, J. L.
dc.contributor.authorTobar, J.
dc.contributor.authorSolar, A.
dc.contributor.authorCampino, C.
dc.contributor.authorArteaga, E.
dc.contributor.authorFardella, C. E.
dc.date.accessioned2025-01-21T01:05:49Z
dc.date.available2025-01-21T01:05:49Z
dc.date.issued2006
dc.description.abstractMultiple endocrine neoplasia type 1 (MEN1) is a syndrome inherited in an autosomal dominant trait caused by the inactivation of the tumor suppressor gene MEN1. Objective: To communicate a family with a new heterozygous germ line mutation in the intronic region of MEN1 gene and to study its influence in the menin expression. Patients and Methods: We studied 5 members of a family with symptomatic hyperparathyroidism (HIPT). One of them had also a neuroendocrine pancreatic tumor, and 2 had non-functional multinodular cortical adrenal hyperplasia compatible with the diagnosis of MEN1. After the mutation was identified, HSP9211 restriction enzyme was used to determine both zygosity and segregation of the mutation. RT-PCR from leukocyte's isolated mRNA and western blot from pancreatic tumor tissue were performed. In vitro studies were done in Chinese hamster ovary (CHO) cells transfected with reporter minigenes carrying the coding regions spanning exon (EX)-intron 9 and EX10 with the mutant and the wild type sequences. Results: We identified a heterozygous G-to-T substitution in the intron-EX junction (IVS9-1 G > T) of MEN1 gene in the index case and the family members. The mRNA from patient's leukocytes was larger (934 bp) in comparison to the normal transcript (717 bp). Immunoblot analysis demonstrated that wild type (67 kDa) and two additional mutant proteins (similar to 55 and similar to 90 kDa) were expressed in the pancreatic tissue. The in vitro study showed a 45% nuclear localization of the mutated menin signal and a 95% in the wild type protein. Conclusions: We identified a new intronic heterozygous germ line mutation (IVS9-1G > T) of MEN1 gene in a family affected by MEN1 syndrome. This mutation alters the splice acceptor site of intron 9 that promotes an incorrect splicing, generating aberrant proteins without the nuclear localization signals necessary for the normal menin translocation to the nucleus.
dc.fuente.origenWOS
dc.identifier.eissn1720-8386
dc.identifier.issn0391-4097
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96025
dc.identifier.wosidWOS:000243547600007
dc.issue.numero10
dc.language.isoen
dc.pagina.final893
dc.pagina.inicio888
dc.revistaJournal of endocrinological investigation
dc.rightsacceso restringido
dc.subjectprimary hyperparathyroidism
dc.subjectMEN1 gene
dc.subjectMEN1 syndrome
dc.subjectmenin
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleNew splicing mutation of <i>MEN1</i> gene affecting the translocation of menin to the nucleous
dc.typeartículo
dc.volumen29
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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