5 research outputs found
Multiple endocrine neoplasia type 2A in two families with the familial medullary thyroid carcinoma associated G533C mutation of the RET proto-oncogene
Introduction: Multiple endocrine neoplasia type 2A (MEN2A) is an
autosomal domin ant hereditary disorder, associated with a cluster of
germline gain-of-function mutations of the RET proto-oncogene (RET),
mainly in exons 10-15. The G533C mutation in exon 8 of the RET is rare
and has been mainly related to the familial medullary thyroid carcinoma.
Patients-methods: We describe the RET G533C mutation in exon 8 of the
RET in two unrelated female index patients, with MEN2A phenotype,
consisting of pheochromocytoma which was the presenting feature and
medullary thyroid carcinoma. In addition, 12 family members were also
studied. DNA extraction, PCR, and sequencing of RET was performed in
exons 7-19 and 21, following standard procedures.
Results: The mutation was found in both index patients and in 6 out of
12 family members (50%). Three of them were biochemically affected with
histologically proven medullary thyroid carcinoma in two of them while
there are no certain clues regarding the other three members as they
declined further evaluation.
Conclusion: Patients with MEN2A should be also searched in exon 8 while
positive carriers of this mutation should be screened annually for
pheochromocytoma or other components of the syndrome
Dilated Cardiomyopathy as the Predominant Feature of Cushing's Syndrome
Cushing’s syndrome, resulting from exposure to excessive amounts of
circulating glucocorticoids, is accompanied with a high mortality risk
mostly due to the cardiovascular complications. Cardiac involvement is
mainly associated with left ventricular hypertrophy. We report the case
of a patient who presented with dilated cardiomyopathy as the
predominant feature Of Cushing’s syndrome, which was fully reversed
after proper Surgical treatment
Embolization as an Alternative Treatment of Insulinoma in a Patient with Multiple Endocrine Neoplasia Type 1 Syndrome
Insulinoma is a rare neuroendocrine tumor, most commonly originating
from the pancreas, which is either sporadic or familial as a component
of multiple endocrine neoplasia type 1 syndrome (MEN1). It is
characterized by increased insulin secretion leading to hypoglycemia.
Surgical removal is considered the treatment of choice, with limited
side effects and relatively low morbidity and mortality, both being
improved by the laparoscopic procedure. We present the case of a
30-year-old patient with MEN1 and recurrent insulinoma with severe
hypoglycemic episodes who could not be surgically treated due to the
adherence of the tumor to large blood vessels and to prior multiple
surgical operations. He was treated by repeated embolization using
spherical polyvinyl alcohol particles, resulting in shrinkage of the
tumor, improvement of the frequency and severity of the hypoglycemic
episodes, and better quality of life
Novel germline mutations of the MEN1 gene in Greek families with multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant
hereditary disorder associated with mutations of the MEN1 gene and
characterized by the combined occurrence of tumours of the parathyroid
glands, the pancreatic islet cells and the anterior pituitary.
To identify MEN1 gene mutations and characterize clinical manifestations
in Greek patients with MEN1.
We studied four unrelated index patients with MEN1, 17 relatives and 100
control subjects. Among the relatives, seven were clinically and/or
biochemically affected, while 10 were unaffected. DNA extraction,
polymerase chain reaction (PCR) and direct sequencing of the MEN1 exons
2-10 and exon/intron boundaries were performed according to standard
procedures.
We identified novel MEN1 gene mutations in three out of four index
patients (75%) and in all affected (100%) relatives. Novel mutations
included: a frameshift mutation in exon 4 (c.684_685insG) at codon 229
(index patient A); a frameshift mutation in exon 8
(c.1160_1170dupAGGAGCGGCCG) involving codons 387-390 (index patient B);
and a missense mutation in exon 4 (c.776T > C), which substitutes
leucine with proline at codon 259 (L259P) (index patient C). In the
fourth index patient, a common polymorphism (D418D) was detected.
This is the first report to reveal a high prevalence of novel MEN1 gene
mutations among Greek MEN1 patients with apparent absence of
genotype-phenotype correlation. Because of the small number of patients
examined, the high prevalence detected might be a chance phenomenon