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

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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Main Authors: 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
Format: Article
Language:English
Published: The Japan Endocrine Society 2025-07-01
Series:Endocrine Journal
Subjects:
ret
ret variant
multiple endocrine neoplasia type 2b
medullary thyroid carcinoma
charcot–marie–tooth disease
Online Access:https://www.jstage.jst.go.jp/article/endocrj/72/7/72_EJ24-0412/_html/-char/en
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Summary: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.
ISSN:1348-4540

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