Intron 9 of MEN1 gene mutation-induced multiple endocrine neoplasia type 1 : one case and analysis of his pedigree

Abstract

To study the MEN1 gene mutations in a multiple endocrine neoplasia type 1 ( MEN 1 ) family,and determine the possible mechanism of disease induced by the mutations.Genomic DNA was isolated from peripheral blood leukocytes and the MEN1-related tumor tissues of the patient and the family members,then the coding exons and exon/intron boundaries of the MEN1 gene were amplified by polymerase chain reaction (PCR) and sequenced.Subclone sequencing was performed to identify the heterozygosity.Further immunohistochemistry was performed to observe menin protein expression in the tumor tissues.We identified a heterozygous deletion mutation of intron 9 ( IVS9+ 1_11 delGTGAGGGACAG) in the proband and two family menbers.We also demonstrated for the first time that the expression of menin protein is absent in the parathyroid adenoma tissue.The heterozygous mutation in the initial of intron 9,IVS9+ 1_11 delGTGAGGGACAG is a new type of MEN1 gene mutations in China.This mutation may produce an aberrant splicing of MEN1 mRNA,generating easily degradation and loss of expression of menin protein and resulting eventually in the disease. Key words: Multiple endocrine neoplasia type 1 ; MEN 1 gene ; Mutation ; Menin protein