A novel recessive splicing mutation in the POU1F1 gene causing combined pituitary hormone deficiency
| العنوان: | A novel recessive splicing mutation in the POU1F1 gene causing combined pituitary hormone deficiency |
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| المؤلفون: | G. Corneli, Patricia Momigliano-Richiardi, Simona Mellone, Mara Giordano, Yari Carlomagno, Daniela Vivenza, Michela Godi, Mariacarolina Salerno, G. Bona, Donatella Capalbo, Luigi Tiradani |
| المساهمون: | Carlomagno, Y., Salerno, Mariacarolina, Vivenza, D., Capalbo, Donatella, Godi, M., Mellone, S., Tiradani, L., Corneli, G., Momigliano Richiardi, P., Bona, G., Giordano, M. |
| المصدر: | Journal of Endocrinological Investigation. 32:653-658 |
| بيانات النشر: | Springer Science and Business Media LLC, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Genetics, Human Growth Hormone, RNA Splicing, Endocrinology, Diabetes and Metabolism, Gene mutation, Biology, Molecular biology, CPHD, In vitro splicing assay, POU1F1, Prolactin, Splicing mutation, Pedigree, Prolactin, Denaturing high performance liquid chromatography, Consanguinity, Pituitary Hormones, Open reading frame, Transactivation, Exon, Endocrinology, RNA splicing, Humans, Female, Allele, Child, Transcription Factor Pit-1, Gene, Gene Deletion |
| الوصف: | Background: Mutations in the gene encoding the pituitary transcription factor POU1F1 (Pit-1, pituitary transcription factor-1) have been described in combined pituitary hormone deficiency (CPHD). Aim: The aim of this study was the characterisation of the molecular defect causing CPHD in a patient born to consanguineous parents. Subject and methods: The case of a 12.5-yr-old girl presenting with severe growth failure at diagnosis (−3 SD score at 3 months) and deficiency of GH, PRL, and TSH was investigated for the presence of POU1F1 gene mutations by denaturing high performance liquid chromatography analysis. Results: A novel mutation adjacent to the IVS2 splicing acceptor site (IVS2-3insA) was identified in the patient at the homozygous state. Analysis of patient’s lymphocyte mRNA and an in vitro splicing assay revealed the presence of 2 aberrant splicing products: a) deletion of the first 71 nucleotides of exon 3, altering the open reading frame and generating a premature stop codon, b) total exon 3 skipping resulting in an in frame deleted mRNA encoding a putative protein lacking part of the transactivation domain and of the POU-specific homeodomain. Notably, the patient’s relatives heterozygous for the mutation had PRL levels under the normal range with no evident clinical symptoms. Conclusions: The IVS2-3insA mutation, responsible for CPHD at the homozygous state, causes the presence of 2 aberrant splicing products encoding non-functional products. In the heterozygotes one normal allele might not guarantee a complete pituitary function. |
| وصف الملف: | STAMPA |
| تدمد: | 1720-8386 0391-4097 |
| DOI: | 10.1007/bf03345736 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56a0ec62c25c6bac5733804f42757960 https://doi.org/10.1007/bf03345736 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....56a0ec62c25c6bac5733804f42757960 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17208386 03914097 |
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| DOI: | 10.1007/bf03345736 |