Fig. 1
Summary data of germline mutations of MENIN in 28 unrelated patients with multiple endocrine neoplasia type 1 in Korea. The positions of the mutations in MENIN are illustrated above respective exons. ATG refers to the start codon; TGA refers to the stop codon.
aMutations were reported as novel in Korea including the present study. Germline mutations (I to IX) that occur with a frequency >1.5% are shown and their respective frequencies (scale shown on the right lower) in the review are indicated by the vertical lines at lower part of the gene [3]. These germline mutations, which collectively represent 20.6% of all reported germline mutations, are: I, c.249_252del GTCT (4.5%); II, c.292C>T (1.5%); III, c.358_360delAAG (1.7%); IV, c.628_631delACAG (2.5%); V, c.784-9G>A (1.9%); VI, c.1243C >T (1.5%); VII, c.1378C>T (2.6%); VIII, c.1546delC (1.8%); IX, c.1546_1547insC (2.7%).
Fig. 2Frequencies of the types of MENIN mutations detected in 28 unrelated patients with multiple endocrine neoplasia type 1. In-frame deletion/insertion was not detected. Gross deletion was not confirmed.
Fig. 3First manifestations of multiple endocrine neoplasia type 1 (MEN1) in Korea. Among 27 symptomatic patients, hyperparathyroidism was documented in 10 patients (37%), pancreas tumors in 10 (37%), and pituitary tumors in three (11%). Four patients (15%) showed less common tumors associated with MEN1 as a first manifestation.
Fig. 4Distinct methylation pattern of hereditary parathyroid tumors compared to respective blood controls (A) and methylation profile of the MENIN gene (B). (A) Heatmap of all differentially methylated genes showing distinct methylation patterns of multiple endocrine neoplasia type 1 (MEN1)-related parathyroid tumors. Heatmap color corresponds to the β-value of the measured CpG-sites. β Ranges from 0 (purely unmethylated, shown in pink) to 1 (purely methylated, shown in green). (B) In this line plot blood average β is indicated by a black line and the parathyroid tissue average β is indicated by a grey line. Significant methylation differences are confined to exon 2 of the MENIN gene: three hypomethylation sites (cg10879244, cg22897141, and cg22527280) are described in the grey box with black arrows. The samples for heatmap are indicated according to specimen (B=blood sample and P=parathyroid tumor); digits after the hyphen denote case numbers as shown in Table 1. DMR, differentially methylated regions.
Table 1Germline Mutations of the MENIN Gene and Clinical Phenotypes in Korea