Germline Mutations of the <i>MEN1</i> Gene in Japanese Kindred with Multiple Endocrine Neoplasia Type 1

Shimizu, Satoko; Tsukada, Toshihiko; Futami, Hitoyasu; Ui, Kotaro; Kameya, Toru; Kawanaka, Masahiro; Uchiyama, Shozo; Aoki, Akira; Yasuda, Hiroko; Kawano, Seiji; Ito, Yukio; Kanbe, Masako; Obara, Takao; Yamaguchi, Ken

doi:10.1111/j.1349-7006.1997.tb00325.x

Cited by 60 publications

(43 citation statements)

References 13 publications

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“…This was contradictory to the previous report showing that no mutation of the MEN1 gene was detected in 5 probands with FHP in the United States and Canada [10]. On the other hand, it has recently been reported that a Japanese patient with FHP had a germline mutation of the MEN1 gene (Y353X in exon 8), although the clinical evaluation for MEN1 was not described in this family [13]. Primary hyperparathyroidism is usually expressed at an early age (85% by age 35) and has a high penetrance (95%) in MEN1 [14].…”

Section: Discussioncontrasting

confidence: 54%

“…The deletion in exon 9 found in our patient predicts the loss of the C-terminal portion of menin. The loss of this portion may be important in the pathogenesis of parathyroid gland hyperplasia, because nine types of mutation in exon 9 have also been reported in MEN1 patients [10,11,13,18]. Very recently, Guru et al [19] have reported that menin is a nuclear protein which has at least 2 independent nuclear localization signals in the C-terminal portion.…”

Section: Discussionmentioning

confidence: 99%

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Germline Mutation of the Multiple Endocrine Neoplasia Type 1(MEN1) Gene in a Family with Primary Hyperparathyroidism.

et al. 1998

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Abstract. Familial primary hyperparathyroidism(FHP) is a rare hereditary disorder characterized by isolated parathyroid tumors without any other lesions related to multiple endocrine neoplasia (MEN). Primary hyperparathyroidism is usually expressed at an early age and is highly penetrated in MEN type 1(MEN1), suggesting that some FHP may be a variant type or early stage of MEN1. The MEN1 gene has recently been cloned and its germline mutations have been considered to play an important role in the tumorigenesis of MEN1. We studied a Japanese family with primary hyperparathyroidism which included 4 patients. To investigate the possible relationship between primary hyperparathyroidism in this family and the MEN1 gene, we analyzed a proband for a germline mutation of the MEN1 gene in this study. We identified a novel heterozygous mutation (1350de13) at codon 414 in exon 9. Restriction digestion analysis revealed the same mutation pattern in his brother with hyperparathyroidism. These findings suggest that our patients may belong to a variant type of MEN1.

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Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Germline Mutation of the Multiple Endocrine Neoplasia Type 1(MEN1) Gene in a Family with Primary Hyperparathyroidism.

et al. 1998

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“…Genomic DNA from leukocytes was extracted and the coding exons and exon-intron boundaries of the MEN1 gene (NM_003977.2) were PCR-amplified and screened by direct sequencing. 8 Moreover, sequencing of the SDHA, SDHAF2, SDHB, SDHC, and SDHD genes (NM_004168.2, NM-017841.1, NM_003000.2, NM_003001.3, NM_003002.2), TMEM127 (NM_017849.1), MAX (NM_002382.3) and CDKN1B gene (NM_004064) were performed on the proband's DNA. The potential effect of the missense variant on menin protein was evaluated in silico using a battery of tools: Polyphen2 (http//:www.genetics.bwh.harvard.edu), UMD predictor, 9 and Alamut 2.2.0 software (Interactive Biosoftware, Rouen, France).…”

Section: Sequencing Analysis Of Genomic Dnamentioning

confidence: 99%

A MEN1 syndrome with a paraganglioma

et al. 2013

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Germline mutations of the MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterized by tumors of the parathyroids, the pancreas, and the anterior pituitary. Paraganglioma (PGL) is a rare endocrine tumor, which can be sporadic or genetically determined. To date, PGL has never been reported as a feature of MEN1. We report here a patient presenting three features of MEN1 syndrome (hyperparathyroidism, pancreatic neuroendocrine tumor, and adrenocortical adenoma) associated with PGL. Genetic analysis of MEN1 gene revealed a new missense mutation in exon 5 (AGG-AAG), causing the substitution of arginine by lysine at codon 275. Screening for other genetic disorders (SDHx, TMEM127, MAX, CDKN1B) causing PGL was negative. Immunohistochemical analyses showed normal levels of succinate dehydrogenase (SDH)A and SDHB in the PGL. The proband's sister, bearing the mutation, had primary hyperparathyroidism. It was the first typical MEN1 syndrome reported with an extra-adrenal PGL.

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“…Although the physiological role of the protein remains under investigation, it has been speculated to suppress tumorigenesis. Recently various heterozygous germline mutations in the MEN1 gene have been identified in cases of MEN1 (10)(11)(12)(13). Here, we report a family with MEN1 whoshowed a mutation of lOOldelC in the proband and his son.…”

Section: Introductionmentioning

confidence: 84%

“…Informed consent was obtained for genetic analysis of the family, and the proband and his two children (a son and a daughter) agreed to be examined. Osaka) and PCR buffer (Takara Shuzo Co.) (10). The initial denaturation was performed for 1 min at 95°C and was followed by 30 cycles of denaturation at 95°C (1 min), annealing at 64-68°C (2 min) and extension at 72°C (1 min) (10 vyVk/w Results Germline mutation analysis PCR amplification and direct sequencing of genomic DNA extracted from the blood of the proband and his son showed a heterozygous germline deletion of cytosine at position bp 1001 in exon 6 of the MEN1 gene (Fig.…”

Section: Case Reportmentioning

confidence: 99%

A Germline Mutation, 1001delC, of the Multiple Endocrine Neoplasia Type 1 (MEN 1) Gene in a Japanese Family.

Wada

Watanabe

Tsukada³

et al. 2001

Intern. Med.

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Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder characterized by tumors of the enteropancreas, parathyroid and anterior pituitary. The MEN1 gene was recently cloned, and germline mutations of the gene have been demonstrated in cases of MEN 1. Here, we report a Japanese family with a germline mutation of the MEN1 gene. The proband (44 y.o., male) had primary hyperparathyroidism (PHP) and pancreatic carcinoid, and his older sister (50 y.o.) had a history of parathyroidectomy for primary hyperparathyrodism at the age of 40. Clinical examination revealed no evidence of PHPor other MEN1-related tumors in his son. Direct sequencing analysis revealed a heterozygous germline mutation (lOOldelC) at codon 297 in exon 6 of the MEN1 gene in the proband and his son. Loss of heterozygosity (LOH) was also found in the resected parathyroid tissue of the proband. The deletion of cytosine 1001 observed in this case induces a frame shift, which causes the appearance of a stop codon (TAG) at codon 367. This mutation appears to be associated with tumors of the endocrine tissues in the cases studied. (Internal Medicine 40: 499-505, 2001)

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Germline Mutations of the MEN1 Gene in Japanese Kindred with Multiple Endocrine Neoplasia Type 1

Cited by 60 publications

References 13 publications

Germline Mutation of the Multiple Endocrine Neoplasia Type 1(MEN1) Gene in a Family with Primary Hyperparathyroidism.

Germline Mutation of the Multiple Endocrine Neoplasia Type 1(MEN1) Gene in a Family with Primary Hyperparathyroidism.

A MEN1 syndrome with a paraganglioma

A Germline Mutation, 1001delC, of the Multiple Endocrine Neoplasia Type 1 (MEN 1) Gene in a Japanese Family.

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