MEN1 935-1G>C Splicing Mutation in an Indian Patient with Multiple Endocrine Neoplasia Type 1
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MEN1 935-1G>C Splicing Mutation in an Indian Patient with Multiple Endocrine Neoplasia Type 1 Rani Raghavan, Sudeep Shah, Altaf A. Kondkar, Alpa J. Dherai, Devendra Desai, Phulrenu Chauhan, Murad Lala and Tester F. Ashavaid Research Laboratories, P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
Abstract
Background and Objective: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized mainly by multiple tumors involving parathyroid, pancreatic, and pituitary glands. To date, there have been no genetic studies reported on MEN1 in the Indian population. In order to begin to establish molecular diagnosis to improve the management of MEN1 in India, we performed a molecular analysis of the MEN1 gene in a patient of Indian origin. Methods: Molecular analysis of the MEN1 gene was performed to identify mutations in an Indian patient previously diagnosed with sporadic MEN1. All the 10 exons of the MEN1 gene were amplified using the polymerase chain reaction and screened by direct DNA sequencing. Results: The DNA sequencing results revealed the presence of an intronic, heterozygous, splicing mutation 935-1G>C in intron 5 of the MEN1 gene. Conclusion: This study provides the first data on genetic analysis of MEN1 in Indian patients.
Background Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome with high penetrance (>95%). It is characterized by the presence of hyperplasia and neoplasia in at least two different endocrine tissues (parathyroid adenomas, entero-pancreatic tumors, and pituitary tumors) within a single patient. Less frequently associated tumors include insulinomas, carcinoids, and acromegaly.[1] Other endocrine and nonendocrine lesions, such as adrenal cortical tumors, multiple lipomas, multiple facial angiofibromas, skin collagenomas, eosophageal leiomyomas, and carcinoids of the bronchi, gastrointestinal tract, and thymus, have also been described, but with a low frequency.[2] MEN1 is a rare condition occurring in one in every 10 000 individuals.[3] However, the incidence of MEN1 in the Asian population still remains to be elucidated.[4] To date, there have been no genetic studies reported on MEN1 in the Indian population.
The gene responsible for MEN1 is the 9Kbp tumor suppressor gene MEN1, located on the q arm of chromosome 11. It consists of 10 exons and encodes a 610 amino acid nuclear protein called menin.[5] The nuclear localization of menin suggests that this protein may have an important role in the regulation of DNA transcription and replication, in the cell cycle, or in the maintenance of genomic integrity. There is increasing evidence that menin may act in DNA repair or synthesis, but the exact mechanism by which menin regulates DNA synthesis or repair in response to DNA damage is currently unknown. To date, >400 different germline and sporadic mutations have been identified across the entire length of the MEN1 gene.[2] Most of t
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