Analysis Of Clinical Features And Gene Mutations In Multiple Endocrine Neoplasia

Objective: To retrospectively analyze the clinical features of patients with multiple endocrine neoplasia(MEN)type 1 and type 2A and to understand the status of diagnosis and treatment of MEN related tumors.The gene test was performed on some MEN1 patients and one MEN2 A pedigree to analyze the relationship between genotype and phenotype and the origin of proband gene.Methods:By collecting case information of 11 MEN-1 patients and 2 MEN-2 patients that were hospitalized from January 2008 to December 2017 in the department of endocrinology of Tianjin Medical University General Hospital,clinical characteristics of MEN-associated parathyroid,pancreatic neuroendocrine,pituitary,carcinoid,medullary thyroid carcinoma and pheochromocytoma were summarized,and the diagnosis and treatment of 13 patients were summarized for clinical diagnosis and treatment reasonable advice.With the informed consent of the patients and their relatives,venous blood was drawn from patients and their families,and DNA was extracted.All exons in all patients with clinically diagnosed MEN1 were amplified by polymerase chain reaction.For patients with no mutations in the MEN1 gene were detected,all exons of CDKN1 B gene were amplified.All exons of RET gene of MEN2 A probands and their family members were amplified,and the amplified products were sequenced and analyzed.According to the results of this study combined with the literature,we summarizes the relationship between gene mutations and clinical phenotypes.Results: 1、Most patients with MEN1 go to our department due to hypoglycemia,pituitary tumor symptoms.10/11(90.91%)patients had hyperparathyroidism,one patient was diagnosed as ectopic parathyroid,and one young woman was genetically diagnosed as MEN1 when she only had hyperparathyroidism performance.All patients received operation of parathyroid had undergone parathyroid adenoma resection and did not undergo total or subtotal parathyroidectomy.One patient of MEN1 with diarrhea was found to have pancreatic neuroendocrine tumors which can secrete calcitonin.Prognosis of patients with MEN-1-related carcinoid is poor.2.The MEN-1 gene mutations were detected in 3 of the 4 MEN-1 patients.The mutation of genes was homozygous mutation c.133G> A(p.E45K),heterozygous mutation c.1546 dup C(p.R516fs),heterozygous mutation c.133G> A(p.E45K),respectively.The mutation of patient 3 is neonatal mutation.No association was found between genotypes and related phenotypes.No MEN1 and CDKN1 B mutations were detected in one patient with a clinical manifestation of MEN-1.3.The MEN 2A proband and other 2 affected patients carried the c.1900 T> C(p.C634R)mutation of the RET protooncogene.Conclusion:1.It is necessary to screen MEN and RET gene mutations in young patients with hyperparathyroidism.At present,clinicians do not know much about the parathyroid standard surgery(total parathyroidectomy or subtotal resection)in patients with MEN.Patients with markedly elevated calcitonin but no thyroid nodule found should be considered for pancreatic neuroendocrine tumors which can secrete calcitonin;thymic carcinoid is one of the major causes of death in MEN-1.2.Patients with MEN-1 clinical phenotype do not always have pathogenic mutations in MEN-1,and may have mutation sites in non-coding regions or large deletions and mutations.If pathogenic mutations are not detected,they should be considered to other genes such as CDKN1 B gene mutations,if necessary,next-generation sequencing(NGS)technology except with or without large deletions or rearrangements.In addition,MEN1 patients with homozygous mutations may show more tumor types than patients with heterozygous mutations.No association between genotypes and phenotypes was found in MEN1 patients.3.The gene mutation of 634 R in the pedigrees of the patient 12 may come from her father.The genotypes and phenotypes of MEN2 A patients are corresponding to each other.However,the time and number of tumors in patients with the same gene mutation in the same family are different.MEN2 A mortality is mainly associated with medullary thyroid carcinoma,early genetic screening is conducive to early intervention to improve the prognosis.