Genetic and clinical analysis in 10 Spanish patients with multiple endocrine neoplasia type 1

Abstract

Multiple endocrine neoplasia type 1 (MEN 1) is characterised by the combination of tumours of the parathyroid, endocrine pancreas and anterior pituitary glands. In 1988 the MEN 1 gene was mapped to chromosome 11q13 and it was cloned in 1997. This gene contains 10 exons and extends across 9 Kb of genomic DNA; it encodes for a product of 610 amino acid named menin whose function is unknown. We have studied 10 unrelated MEN 1 kindreds by a complete sequencing analysis of the entire gene; mutations were identified in nine of them: five deletions, one insertion, two nonsense mutation and a complex alteration consisting of a deletion and an insertion that can be explained by a hairpin loop model. Two of the mutations have been previously described; the other seven were novel, and they were scattered throughout the coding sequence of the gene. As in previous series, no correlation was found between phenotype and genotype.

Mutational and gross deletion study of the MEN1 gene and correlation with clinical features in Spanish patients

“…Each family showed a different alteration and 10 out of 25 mutations had not been previously described (40%) (table 1). Some of these results have been partly described by Cebrián et al 19 Three of them generated a change of amino acid: H139P (F38), E45K (F52), and A49F (F64). In order to rule out that the missense mutations not previously described (H139P and A49F) were benign polymorphisms, we performed the study in 200 independent alleles of the control population by means of CSGE and these variants were not present, suggesting the pathogenic character of the change.…”

A rapid and easy method for multiple endocrine neoplasia type 1 mutation detection using conformation-sensitive gel electrophoresis

“…2). Nine of them had been reported by Cebrián et al (1999): 5 deletions in exons 2 and 10; 1 insertion in exon 2; 1 insertion/deletion in exon 4; 2 nonsense mutations in exons 3 and 7. The remaining two patients had previously described alterations: a polymorphism in codon 541 (Chandrasekharappa et al 1997;Agarwal et al 1997;Sato et al 1998;Tanaka et al 1998) and a nucleotide substitution in the donor site of a splice in intron 6 (Mutch et al 1999).…”

“…The nine coding exons of the MEN1 gene were amplified with oligonucleotide primers under conditions previously described (European Consortium on MEN1 1997; Cebrián et al 1999). We optimized four multiplex amplifications to hasten the CSGE analysis: exon 2 ϩ exon 5-6, exon 3 ϩ exon 10, exon 7 ϩ exon 8, and exon 9 ϩ exon 4.…”

“…Eleven of those patients had been already tested by our group by SSCP and/or sequencing analysis, and the results of some of these tests were previously published (Cebrián et al 1999). The remaining group of patients was referred to our center in order to confirm the suspected clinical diagnosis and to perform a carrier diagnosis in all families.…”

Genetic Aspects of Familial Thyroid Cancer

“…Although thyroid adenomas and lipomas all can occur [2,3], there is no major malignant thyroid involvement in MEN-1 (see [1][2][3][4] for further details).…”