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Impact of a novel 14 bp MEN1 deletion in a patient with hyperparathyroidism and gastrinoma

Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease characterized by tumors in endocrine and/or non endocrine organs due to mutations in MEN1 encoding a nuclear scaffold protein‘menin’ involved in regulation of different cellular activities. We report a novel 14 bp MEN1...

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Autores principales: Birla, Shweta, P Jyotsna, Viveka, Singla, Rajiv, Tripathi, Madhavi, Sharma, Arundhati
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482156/
https://www.ncbi.nlm.nih.gov/pubmed/26191410
http://dx.doi.org/10.1530/EDM-15-0011
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author Birla, Shweta
P Jyotsna, Viveka
Singla, Rajiv
Tripathi, Madhavi
Sharma, Arundhati
author_facet Birla, Shweta
P Jyotsna, Viveka
Singla, Rajiv
Tripathi, Madhavi
Sharma, Arundhati
author_sort Birla, Shweta
collection PubMed
description Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease characterized by tumors in endocrine and/or non endocrine organs due to mutations in MEN1 encoding a nuclear scaffold protein‘menin’ involved in regulation of different cellular activities. We report a novel 14 bp MEN1 deletion mutation in a 35-year-old female with history of recurrent epigastric pain, vomiting, loose stools and weight loss. On evaluation she was diagnosed to have multifocal gastro-duodenal gastrinoma with paraduodenal lymph nodes and solitary liver metastasis. She was also found to have primary hyperparathyroidism with bilateral inferior parathyroid adenoma. Pancreatico-duodenectomy with truncalvagotomy was performed. Four months later, radiofrequency ablation (RFA) of segment 4 of the liver was done followed by three and a half parathyroidectomy. MEN1 screening was carried out for the patient and her family members. MEN-1 sequencing in the patient revealed a heterozygous 14 bp exon 8 deletion. Evaluation for pathogenicity and protein structure prediction showed that the mutation led to a frameshift thereby causing premature termination resulting in a truncated protein. To conclude, a novel pathogenic MEN1 deletion mutation affecting its function was identified in a patient with hyperparathyroidism and gastrinoma. The report highlights the clinical consequences of the novel mutation and its impact on the structure and function of the protein. It also provides evidence for co-existence of pancreatic and duodenal gastrinomas in MEN1 syndrome. MEN1 testing provides important clues regarding etiology and therefore should be essentially undertaken in asymptomatic first degree relatives who could be potential carriers of the disease. LEARNING POINTS: Identification of a novel pathogenic MEN1 deletion mutation. MEN1 mutation screening in patients with pituitary, parathyroid and pancreatic tumors, and their first degree relatives gives important clues about the etiology. Pancreatic and duodenal gastrinomas may co-exist simultaneously in MEN1 syndrome.
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spelling pubmed-44821562015-07-17 Impact of a novel 14 bp MEN1 deletion in a patient with hyperparathyroidism and gastrinoma Birla, Shweta P Jyotsna, Viveka Singla, Rajiv Tripathi, Madhavi Sharma, Arundhati Endocrinol Diabetes Metab Case Rep Insight into Disease Pathogenesis or Mechanism of Therapy Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease characterized by tumors in endocrine and/or non endocrine organs due to mutations in MEN1 encoding a nuclear scaffold protein‘menin’ involved in regulation of different cellular activities. We report a novel 14 bp MEN1 deletion mutation in a 35-year-old female with history of recurrent epigastric pain, vomiting, loose stools and weight loss. On evaluation she was diagnosed to have multifocal gastro-duodenal gastrinoma with paraduodenal lymph nodes and solitary liver metastasis. She was also found to have primary hyperparathyroidism with bilateral inferior parathyroid adenoma. Pancreatico-duodenectomy with truncalvagotomy was performed. Four months later, radiofrequency ablation (RFA) of segment 4 of the liver was done followed by three and a half parathyroidectomy. MEN1 screening was carried out for the patient and her family members. MEN-1 sequencing in the patient revealed a heterozygous 14 bp exon 8 deletion. Evaluation for pathogenicity and protein structure prediction showed that the mutation led to a frameshift thereby causing premature termination resulting in a truncated protein. To conclude, a novel pathogenic MEN1 deletion mutation affecting its function was identified in a patient with hyperparathyroidism and gastrinoma. The report highlights the clinical consequences of the novel mutation and its impact on the structure and function of the protein. It also provides evidence for co-existence of pancreatic and duodenal gastrinomas in MEN1 syndrome. MEN1 testing provides important clues regarding etiology and therefore should be essentially undertaken in asymptomatic first degree relatives who could be potential carriers of the disease. LEARNING POINTS: Identification of a novel pathogenic MEN1 deletion mutation. MEN1 mutation screening in patients with pituitary, parathyroid and pancreatic tumors, and their first degree relatives gives important clues about the etiology. Pancreatic and duodenal gastrinomas may co-exist simultaneously in MEN1 syndrome. Bioscientifica Ltd 2015-04-29 2015 /pmc/articles/PMC4482156/ /pubmed/26191410 http://dx.doi.org/10.1530/EDM-15-0011 Text en © 2015 The authors This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en_GB) .
spellingShingle Insight into Disease Pathogenesis or Mechanism of Therapy
Birla, Shweta
P Jyotsna, Viveka
Singla, Rajiv
Tripathi, Madhavi
Sharma, Arundhati
Impact of a novel 14 bp MEN1 deletion in a patient with hyperparathyroidism and gastrinoma
title Impact of a novel 14 bp MEN1 deletion in a patient with hyperparathyroidism and gastrinoma
title_full Impact of a novel 14 bp MEN1 deletion in a patient with hyperparathyroidism and gastrinoma
title_fullStr Impact of a novel 14 bp MEN1 deletion in a patient with hyperparathyroidism and gastrinoma
title_full_unstemmed Impact of a novel 14 bp MEN1 deletion in a patient with hyperparathyroidism and gastrinoma
title_short Impact of a novel 14 bp MEN1 deletion in a patient with hyperparathyroidism and gastrinoma
title_sort impact of a novel 14 bp men1 deletion in a patient with hyperparathyroidism and gastrinoma
topic Insight into Disease Pathogenesis or Mechanism of Therapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482156/
https://www.ncbi.nlm.nih.gov/pubmed/26191410
http://dx.doi.org/10.1530/EDM-15-0011
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