p.M918W, a novel RET germline variant: a case report and literature review of the possible association of multiple endocrine neoplasia type 2B and Charcot-Marie-Tooth disease
Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal dominant disorder caused by germline pathogenic RET variants. On the other hand, Charcot–Marie–Tooth disease (CMT) is a hereditary neurological disorder, characterized by distal muscle weakness and sensory loss, with approximately 100...
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The Japan Endocrine Society
2025-07-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/72/7/72_EJ24-0412/_html/-char/en |
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| author | Mami Sato Rei Kubota Shinya Uchino Takayuki Morita Ryoyu Niikuni Teruhisa Udagawa Yoshiya Hagiwara Miyako Tanaka Miku Sato Yuta Tezuka Kei Omata Yoshikiyo Ono Kazuhiro Haginoya Noriaki Nakashima Keisei Fujimori Takanori Ishida |
| author_facet | Mami Sato Rei Kubota Shinya Uchino Takayuki Morita Ryoyu Niikuni Teruhisa Udagawa Yoshiya Hagiwara Miyako Tanaka Miku Sato Yuta Tezuka Kei Omata Yoshikiyo Ono Kazuhiro Haginoya Noriaki Nakashima Keisei Fujimori Takanori Ishida |
| author_sort | Mami Sato |
| collection | DOAJ |
| description | Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal dominant disorder caused by germline pathogenic RET variants. On the other hand, Charcot–Marie–Tooth disease (CMT) is a hereditary neurological disorder, characterized by distal muscle weakness and sensory loss, with approximately 100 identified causative genes. Herein, we report a de novo RET mutation in a patient presenting with clinical features of both MEN2B and CMT. The patient, a 22-year-old woman, had a history of lower limb muscle weakness, with no family history of MEN2B or CMT. The patient was being treated for a thyroid gland neoplasm. Genetic testing of the medullary thyroid carcinoma revealed a previously unreported RET germline variant, p.M918W (RET: c.2752_2753delinsTG, p.Met918Trp). The novel p.M918W RET variant was associated with concurrent MEN2B and CMT. This finding was unexpected as MEN2B typically manifests with distinct features, such as marfanoid habitus and mucosal neuromas, but not with muscle weakness, as seen in CMT. Based on this finding, the plausible role of the p.M918W mutation as a shared pathway for both MEN2B and CMT warrants further investigation. |
| format | Article |
| id | doaj-art-c386332df6884f048d01b15a3f69c4fc |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-c386332df6884f048d01b15a3f69c4fc2025-08-20T03:28:19ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402025-07-0172783984510.1507/endocrj.EJ24-0412endocrjp.M918W, a novel RET germline variant: a case report and literature review of the possible association of multiple endocrine neoplasia type 2B and Charcot-Marie-Tooth diseaseMami Sato0Rei Kubota1Shinya Uchino2Takayuki Morita3Ryoyu Niikuni4Teruhisa Udagawa5Yoshiya Hagiwara6Miyako Tanaka7Miku Sato8Yuta Tezuka9Kei Omata10Yoshikiyo Ono11Kazuhiro Haginoya12Noriaki Nakashima13Keisei Fujimori14Takanori Ishida15Department of Surgery, Tohoku University Hospital, Sendai, Miyagi 980-8574, JapanHachinohe City Hospital, Hachinohe, Aomori 031-8555, JapanDepartment of Endocrine Surgery, Noguchi Thyroid Clinic and Hospital Foundation, Beppu, Oita 874-0902, JapanDepartment of Surgery, Tohoku University Hospital, Sendai, Miyagi 980-8574, JapanDepartment of Surgery, Tohoku University Hospital, Sendai, Miyagi 980-8574, JapanDepartment of Surgery, Suifu Hospital, Mito, Ibaraki 311-4141, JapanDepartment of Surgery, Tohoku University Hospital, Sendai, Miyagi 980-8574, JapanDepartment of Surgery, Tohoku University Hospital, Sendai, Miyagi 980-8574, JapanDepartment of Surgery, Tohoku University Hospital, Sendai, Miyagi 980-8574, JapanDepartment of Diabetes, Metabolism and Endocrinology, Tohoku University Hospital, Sendai, Miyagi 980-8574, JapanDepartment of Diabetes, Metabolism and Endocrinology, Tohoku University Hospital, Sendai, Miyagi 980-8574, JapanDepartment of Diabetes, Metabolism and Endocrinology, Tohoku University Hospital, Sendai, Miyagi 980-8574, JapanDepartment of Pediatric Neurology, Miyagi Children’s Hospital, Sendai, Miyagi 989-3126, JapanDepartment of Surgery, Suifu Hospital, Mito, Ibaraki 311-4141, JapanDepartment of Surgery, Tohoku University Hospital, Sendai, Miyagi 980-8574, JapanDepartment of Surgery, Tohoku University Hospital, Sendai, Miyagi 980-8574, JapanMultiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal dominant disorder caused by germline pathogenic RET variants. On the other hand, Charcot–Marie–Tooth disease (CMT) is a hereditary neurological disorder, characterized by distal muscle weakness and sensory loss, with approximately 100 identified causative genes. Herein, we report a de novo RET mutation in a patient presenting with clinical features of both MEN2B and CMT. The patient, a 22-year-old woman, had a history of lower limb muscle weakness, with no family history of MEN2B or CMT. The patient was being treated for a thyroid gland neoplasm. Genetic testing of the medullary thyroid carcinoma revealed a previously unreported RET germline variant, p.M918W (RET: c.2752_2753delinsTG, p.Met918Trp). The novel p.M918W RET variant was associated with concurrent MEN2B and CMT. This finding was unexpected as MEN2B typically manifests with distinct features, such as marfanoid habitus and mucosal neuromas, but not with muscle weakness, as seen in CMT. Based on this finding, the plausible role of the p.M918W mutation as a shared pathway for both MEN2B and CMT warrants further investigation.https://www.jstage.jst.go.jp/article/endocrj/72/7/72_EJ24-0412/_html/-char/enretret variantmultiple endocrine neoplasia type 2bmedullary thyroid carcinomacharcot–marie–tooth disease |
| spellingShingle | Mami Sato Rei Kubota Shinya Uchino Takayuki Morita Ryoyu Niikuni Teruhisa Udagawa Yoshiya Hagiwara Miyako Tanaka Miku Sato Yuta Tezuka Kei Omata Yoshikiyo Ono Kazuhiro Haginoya Noriaki Nakashima Keisei Fujimori Takanori Ishida p.M918W, a novel RET germline variant: a case report and literature review of the possible association of multiple endocrine neoplasia type 2B and Charcot-Marie-Tooth disease Endocrine Journal ret ret variant multiple endocrine neoplasia type 2b medullary thyroid carcinoma charcot–marie–tooth disease |
| title | p.M918W, a novel RET germline variant: a case report and literature review of the possible association of multiple endocrine neoplasia type 2B and Charcot-Marie-Tooth disease |
| title_full | p.M918W, a novel RET germline variant: a case report and literature review of the possible association of multiple endocrine neoplasia type 2B and Charcot-Marie-Tooth disease |
| title_fullStr | p.M918W, a novel RET germline variant: a case report and literature review of the possible association of multiple endocrine neoplasia type 2B and Charcot-Marie-Tooth disease |
| title_full_unstemmed | p.M918W, a novel RET germline variant: a case report and literature review of the possible association of multiple endocrine neoplasia type 2B and Charcot-Marie-Tooth disease |
| title_short | p.M918W, a novel RET germline variant: a case report and literature review of the possible association of multiple endocrine neoplasia type 2B and Charcot-Marie-Tooth disease |
| title_sort | p m918w a novel ret germline variant a case report and literature review of the possible association of multiple endocrine neoplasia type 2b and charcot marie tooth disease |
| topic | ret ret variant multiple endocrine neoplasia type 2b medullary thyroid carcinoma charcot–marie–tooth disease |
| url | https://www.jstage.jst.go.jp/article/endocrj/72/7/72_EJ24-0412/_html/-char/en |
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