ESPE Abstracts (2019) 92 P3-186

Variable Expressivity in Three Generation from a Colombian Family with Multiple Endocrine Neoplasia with Mutation c.482G>A (p.Gly161Asp) in the Gene MEN1 not Described in Colombia

Liliana Mejia de Beldjenna 1,2,3,4, Lorena Diaz3, Sara Vanegas3, Lina Perafan3, Harry Pachajoa5,6


1Fundation Clinic Valle del Lili, Cali, Colombia. 2Fundation Clinic Club Noel, Cali, Colombia. 3Universidad ICESI, Cali, Colombia. 4Universidad Libre GRINPEDN, Cali, Colombia. 5Universidad ICESI, cali, Colombia. 6Fundation Clinic Valle del Lili, cali, Colombia


Introduction: Multiple endocrine neoplasia type 1 is an autosomal illness dominant caused by mutations in the gene menina (MEN1) with high penetrance, characterized by neoplasia parathyroid glands, anterior pituitary, endocrine pancreas and duodenum. Although it has been associated with other types of cancer like breast cancer.

Methods and materials: Clinical analysis, mutational and sequencing report Sanger from gene MEN1 are reported to 6 patients with neoplasia within a large family 15 members (three generations), with 8 members affected.

Outcomes:

GenderAgeFirst TumorHipophysisThymomaWindpipe or LungPancreasMutation p.Gly161Asp
M10ParathyroidProlactinoma+
F9Parathyroid+
F40ParathyroidAdenoma+++
M28ParathyroidGrowth Hormone Prolactin++
M46ND+ND
M44ND+Died
F75Parathyroid+
M53Parathyroid+
M: Male F: Female ND: not determined

Analysis and conclusions: The 66% of the adults population debuted with parathyroid pathology. And the 100% of the children affected. The 33% of the adults showed timoma.

The presence of the c.482G>A (p.Gly161Asp) mutation in MEN1 gene were confirmed by Sanger sequencing in all patients. Therefore, this family with hereditary multiple endocrine neoplasia demonstrate an autosomal dominant inheritance with complete penetrance and high expressivity and is recommend to look always for a parathyroid affection as the first demonstration in the carriers.

All the bioinformatic tools used to predict the mutation effect indicates that the substitution of glycine for aspartic acid at position 161 of MEN1, potentially affect protein structure and function since it is an aminoacid highly conserved between species and is located in a region of interaction with important proteins for the regulation of gene transcription and the progression of the cell cycle, which demonstrates the pathogenic potential of the variant. Although this mutation in MEN1 gene was previously reported by one single japanese family, it has not been described in Colombia.

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