The Study Of Clinical Phenotype And Gene Mutation In Patients With Multiple Endocrine Neoplasia Type1

ObjectivesMultiple endocrine neoplasia type 1(MEN1) is an autosomal dominant familial disorder characterized by combined occurrence of tumors of parathyroid glands, enteropancreatic and the anterior pituitary, which is due to MEN1 gene mutation. The MEN1 gene is localized at chromosomal 11q13 and spans 9kb of the genome,and encodes a 610 amino acids protein termed " menin ", which participates in regulating cell division,genome stability and transcription as a tumor suppressor.Germline mutational analysis was taken for MEN1 gene with the aim of: (1)clarifying the genotype of these three sporadic MEN1 patients; (2)exploring the genetic tumorigenesis mechanism; (3)clarifying if their first-degree relatives had MEN1 gene mutation, and giving the suggestion about treatment and follow-up.Subjects and MethodsThree sporadic MEN1 patients and their relatives were enrolled in the study. Genome DNA was extracted from peripheral blood leucocytes and used with the previous reported 8 pairs of primers of PCR of 9 exons of MEN1 gene and their responding intron/exon boundaries. The DNA sequence of gel purified PCR products were determined.Sequences were compared with genome DNA and cDNA sequences in the UCSC website through internet. DNA sequences abnormality was inquired in the HGMD website. Give proband B without MEN1 mutation other gene(such RET, CDNK1B, CDC75 gene and so on) testing.Results1. The entire coding region of the MEN1 gene of proband B and her father were analyzed by direct sequencing. A heterozygote C to A transition was detected in c.984 within exon 7, which has previously been reported.2. Using the same methods,the entire coding region of the MEN1 gene of proband A and C were analyzed,no mutation was detected, and subsequently we detected RET, CDKN1B, CDC75 gene, but we did not find any mutation in the coding region and adjacent splice sites.Conclusions1. A MEN1 pedigree was identified, and the mutation of c.984C>A(p.Y328*) in MEN1 gene is one type of MEN gene mutations. We also provide a testing strategy for the MEN1 patient without MEN1 mutation.2. The genetic molecular mechanism of sporadic multiple endocrine neoplasia still need further study...