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

Birla S, P Jyotsna V, Singla R, Tripathi M, Sharma A - Endocrinol Diabetes Metab Case Rep (2015)

Bottom Line: She was also found to have primary hyperparathyroidism with bilateral inferior parathyroid adenoma.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cyto-Molecular Genetics, Department of Anatomy , All India Institute of Medical Sciences , New Delhi 110029 , India.

ABSTRACT

Unlabelled: 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.

No MeSH data available.


Related in: MedlinePlus

Showing structural analysis of the novel 14 bp deletion MEN1 mutation. (A) Normal MEN1 protein. (B) Mutant MEN1 protein with premature truncation. The deletion causing frameshift leading to altered amino acid sequence (shown in red C). The superimposed structural analysis of the normal and the truncated mutant protein.
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fig3: Showing structural analysis of the novel 14 bp deletion MEN1 mutation. (A) Normal MEN1 protein. (B) Mutant MEN1 protein with premature truncation. The deletion causing frameshift leading to altered amino acid sequence (shown in red C). The superimposed structural analysis of the normal and the truncated mutant protein.

Mentions: Direct sequencing of the MEN-1 gene in the patient revealed a heterozygous 14 bp deletion mutation in exon 8 (Fig. 2). Evaluation for pathogenicity using MutationT@ster was in concordance with the structural analysis (5) which showed that the mutation leads to frameshift thereby causing premature termination of mRNA resulting into a truncated protein product (Fig. 3). Screening the family members revealed absence of the mutation in them.


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

Birla S, P Jyotsna V, Singla R, Tripathi M, Sharma A - Endocrinol Diabetes Metab Case Rep (2015)

Showing structural analysis of the novel 14 bp deletion MEN1 mutation. (A) Normal MEN1 protein. (B) Mutant MEN1 protein with premature truncation. The deletion causing frameshift leading to altered amino acid sequence (shown in red C). The superimposed structural analysis of the normal and the truncated mutant protein.
© Copyright Policy - license
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482156&req=5

fig3: Showing structural analysis of the novel 14 bp deletion MEN1 mutation. (A) Normal MEN1 protein. (B) Mutant MEN1 protein with premature truncation. The deletion causing frameshift leading to altered amino acid sequence (shown in red C). The superimposed structural analysis of the normal and the truncated mutant protein.
Mentions: Direct sequencing of the MEN-1 gene in the patient revealed a heterozygous 14 bp deletion mutation in exon 8 (Fig. 2). Evaluation for pathogenicity using MutationT@ster was in concordance with the structural analysis (5) which showed that the mutation leads to frameshift thereby causing premature termination of mRNA resulting into a truncated protein product (Fig. 3). Screening the family members revealed absence of the mutation in them.

Bottom Line: She was also found to have primary hyperparathyroidism with bilateral inferior parathyroid adenoma.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cyto-Molecular Genetics, Department of Anatomy , All India Institute of Medical Sciences , New Delhi 110029 , India.

ABSTRACT

Unlabelled: 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.

No MeSH data available.


Related in: MedlinePlus