Preimplantation Genetic Diagnosis of Multiple Endocrine Neoplasia Type 2A Using Informative Markers Identified by Targeted Sequencing

Chen, Songchang; Li, Shuyuan; Zhang, Junyu; Zhang, Lanlan; Chen, Yiyao; Wang, Li; Jin, Li; Hu, Yuting; Qi, Xiao-Ping; Huang, He‐Feng; Xu, Chenming

doi:10.1089/thy.2017.0200

Cited by 17 publications

(19 citation statements)

References 28 publications

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“…regarding pregnancy termination (37). Compared to timely prophylactic thyroidectomy (PTT, discussed below), PGT-M is a primary prevention strategy which can avoid the transmission of diseases and families at risk from the source (38). However, the potential risk (such as implantation failure, multiple pregnancies, premature birth, etc.…”

Section: Prevention Of Men2mentioning

confidence: 99%

“…As demonstrated in the ATA-2015, the clinicians should make patients aware of both the benefits and the potential risks of these technologies, and genetic counseling about these reproductive options should be considered for all patients carrying the RET mutations who are of reproductive age, particularly those having RET mutations in codons 634 and 918 (2). A simple and efficient method that involves targeted and capture-based next generation sequencing (T-NGS) for identification of informative markers including the entire RET coding region and 1 Mb range on each side of the gene together with Sanger sequencing has been established by our group for PGT-M of MEN2 (38). Using this method, one healthy baby whose father had MEN2A with the RET C634Y mutation was born without the inheritance of the mutation.…”

Section: Prevention Of Men2mentioning

confidence: 99%

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5P Strategies for Management of Multiple Endocrine Neoplasia Type 2: A Paradigm of Precision Medicine

Ding

et al. 2020

Front. Endocrinol.

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Multiple endocrine neoplasia type 2 (MEN2) is a neuroendocrine cancer syndrome characterized by medullary thyroid carcinoma, in combination or not with pheochromocytoma, hyperparathyroidism, and extra-endocrine features. MEN2 syndrome includes two clinically distinct forms subtyped as MEN2A and MEN2B. Nearly all MEN2 cases are caused by germline mutations of the RET proto-oncogene. In this review, we propose "5P" strategies for management of MEN2: prevention, prediction, personalization, psychological support, and participation, which could effectively improve clinical outcomes of patients. Based on RET mutations, MEN2 could be prevented through prenatal diagnosis or preimplantation genetic testing. Identification of pathogenic mutations in RET can enable early diagnosis of MEN2. Combining RET mutation testing with measurement of serum calcitonin, plasma or urinary metanephrine/normetanephrine, and serum parathyroid hormone levels could allow risk stratification and accurately prediction of MEN2 progression, thus facilitating implementation of personalized precision treatments to increase disease-free survival and overall survival. Furthermore, increased awareness of MEN2 is needed, which requires participation of physicians, patients, family members, and related organizations. Psychological support is also important for patients with MEN2 to promote comprehensive management of MEN2 symptoms. The "5P" strategies for management of MEN2 represent a typical clinical example of precision medicine. These strategies could effectively improve the health of MEN2 patient, and avoid adverse outcomes, including death and major morbidity, from MEN2.

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Section: Prevention Of Men2mentioning

confidence: 99%

Section: Prevention Of Men2mentioning

confidence: 99%

5P Strategies for Management of Multiple Endocrine Neoplasia Type 2: A Paradigm of Precision Medicine

Ding

et al. 2020

Front. Endocrinol.

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“…In 2011, Altarescu et al reported of an Israeli woman with MEN 2A, who by the use of PGT-M, gave birth to genetically unaffected dizygotic twins (8). Chen et al presented a similar case of PGT-M in a Chinese couple where the male had MEN 2A (9). Unlike some other countries, in Denmark PGT is not reserved for specific diseases for which the procedure has been approved (19,20).…”

Section: Discussionmentioning

confidence: 99%

“…Adding to this, patients seem to have a genuine interest in PGT-M in relation to reproduction ( 7 ). However, just two cases have been reported so far and none originated from Europe ( 8 , 9 ). Aiming to increase awareness among physicians treating this and other genetic disorders, especially in Europe, of the possibility for PGT-M in MEN 2A patients, we here report the first European case.…”

Section: Introductionmentioning

confidence: 99%

Preimplantation Genetic Testing of Multiple Endocrine Neoplasia Type 2A

et al. 2020

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Background: When discussing matters of reproduction, the 2015 revised guidelines for the management of medullary thyroid carcinoma recommend that patients diagnosed with multiple endocrine neoplasia type 2A (MEN 2A) are informed about the option of Preimplantation Genetic Testing for Monogenic Disorders (PGT-M). In addition, patients seem to have a genuine interest in reproductive options. However, there are just two reports worldwide of this technology being used for patients with MEN 2A. We here present, in a Danish couple where the man has MEN 2A, the first European family with children born after PGT-M. Objective: To report the results of PGT-M in relation to multiple endocrine neoplasia type 2A with the aim to increase awareness among physicians treating this and other genetic disorders. Methods: A Danish couple was referred to the PGT Center at Copenhagen University Hospital Rigshospitalet and opted for PGT-M after counseling by a clinical geneticist and a fertility doctor. The embryos were diagnosed using microsatellite polymorphic marker close to RET. Results: The couple had two healthy children born in 2017 and 2019 as a result of a total of three ICSI treatments including controlled ovarian stimulation, oocyte retrieval and PGT-M, and a total of six blastocyst transfers. Conclusion: A session with a clinical geneticist covering all reproductive options for patients in early adult life is a relevant part of the clinical management of patients with MEN 2A, and other patients with hereditary cancer predisposition syndromes.

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“…This includes individuals with a pre‐existing genetic diagnosis, carriers of disease‐associated mutations or parents in whom previous pregnancies or offspring have been affected by genetic disease. Increasingly, pre‐implantation genetic diagnosis (PGD) may be offered in situations where parents are at risk of transmitting severe monogenic disorders and has been successfully employed in the context of MEN1, MEN2 and CAH . PGD is only possible in the context of in vitro fertilization (IVF) and involves the sequencing of DNA isolated from a small number of early blastocyst cells .…”

Section: Special Situations For Testingmentioning

confidence: 99%

Clinical genetic testing in endocrinology: Current concepts and contemporary challenges

Newey

2019

Clinical Endocrinology

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Recent advances in DNA sequencing technology have led to an unprecedented period of disease‐gene discovery offering many new opportunities for genetic testing in the clinical setting. Endocrinology has seen a rapid expansion in the taxonomy of monogenic disorders, which can be detected by an expanding portfolio of genetic tests in both diagnostic and predictive settings. Successful testing relies on many factors including the ability to identify those at increased risk of genetic disease in the busy clinic as well as a working knowledge of the various testing platforms and their limitations. The clinical utility of a given test is dependent upon many factors, which include the reliability of the genetic testing platform, the accuracy of the test result interpretation and knowledge of disease penetrance and expression. The increasing adoption of “high‐content” genetic testing based on next‐generation sequencing (NGS) to diagnose hereditary endocrine disorders brings a number of challenges including the potential for uncertain test results and/or genetic findings unrelated to the indication for testing. Therefore, it is increasingly important that the clinician is aware of the current evolution in genetic testing, and understands the different settings in which it may be employed. This review provides an overview of the genetic testing workflow, focusing on each of the major components required for successful testing in adult and paediatric endocrine settings. In addition, the challenges of variant interpretation are highlighted, as are issues related to informed consent, prenatal diagnosis and predictive testing. Finally, the future directions of genetic testing relevant to endocrinology are discussed.

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Preimplantation Genetic Diagnosis of Multiple Endocrine Neoplasia Type 2A Using Informative Markers Identified by Targeted Sequencing

Abstract: Targeted, capture-based next-generation sequencing for identification of informative markers together with Sanger sequencing is an easy and efficient method for the PGD of monogenic diseases such as MEN2.

Cited by 17 publications

References 28 publications

5P Strategies for Management of Multiple Endocrine Neoplasia Type 2: A Paradigm of Precision Medicine

5P Strategies for Management of Multiple Endocrine Neoplasia Type 2: A Paradigm of Precision Medicine

Preimplantation Genetic Testing of Multiple Endocrine Neoplasia Type 2A

Clinical genetic testing in endocrinology: Current concepts and contemporary challenges

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