title: Case report: a p.C618S RET proto-oncogene germline mutation in a large Chinese pedigree with familial medullary thyroid carcinoma.
abstract: We report a Chinese pedigree with familial medullary thyroid carcinoma. Direct sequencing of the entire coding sequences of Rearranged during Transfection (RET) identified a recurrent c.T1852A (p.C618S) mutation in 13 of 23 members. The polymorphisms c.A135G (p.A45A), c.A1296G (p.A432A), c.T2307G (p.L769L) and IVS19 + 15T > C were also found in 13 carriers, and c.G2073A (p.G691S) was found in 1 carrier. Of the 13 carriers, seven (mean age: 42.6 years, range: 27-64) presented MTC as the isolated clinical phenotype, with elevated basal serum calcitonin (average: 1077.9 ng/L, range: 504-2,652) and a mean diameter of thyroid nodules of 2.97 cm (range: 1.6-4.3); they underwent a total thyroidectomy with modified bilateral/unilateral neck dissection and/or level VI lymph node dissection. The other 6 carriers did not accept surgery (4 rejected, 2 awaited). These were 2 older patients (63 and 32 years) with elevated calcitonin (1359 and 41.4 ng/L) and multi-centric hypoechoic nodules (1.5 and 0.6 cm) with calcifications in both/left thyroid lobes; and Doppler ultrasound showed normal bilateral thyroids in 4 younger carriers (median age: 8.3 years, range: 4-12) but with increased calcitonin (average: 9.7 ng/L, range: 7.87-12.2) in 3 of them. The phenotype here is consistent with the clinical symptoms reported worldwide. We recommend that screening of hotspot regions of RET should be preferentially carried out, while whole-exon sequencing should be performed when clinical signs fail to reveal hotspot mutations or different phenotype discrepancies. Moreover, we strongly suggest prophylactic thyroidectomy should be performed before age 5 in carriers with p.C618S to prevent the occurrence and metastasis of MTC.
authors: Departments of Urologic and Oncologic Surgery and Department of Pathology, The 117th PLA Hospital, 40 Jichang Road, Hangzhou, 310004, Zhejiang, China. qxplmd@vip.sina.com
authors: X-P
authors: XP
authors: Qi
authors: R-B
authors: RB
authors: Ying
authors: J-M
authors: JM
authors: Ma
authors: W-T
authors: WT
authors: Liu
authors: Z-F
authors: ZF
authors: Du
authors: J
authors: J
authors: Fei
authors: C-P
authors: CP
authors: Yang
authors: Q-Z
authors: QZ
authors: Song
authors: H-Y
authors: HY
authors: Jin
authors: Z-G
authors: ZG
authors: Chen
authors: J-S
authors: JS
authors: Han
authors: J-Q
authors: JQ
authors: Wang
authors: X-L
authors: XL
authors: Chen
authors: Y
authors: Y
authors: Zhao
authors: J-J
authors: JJ
authors: Lu
authors: X-N
authors: XN
authors: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D018276:Carcinoma, Medullary / Q000151:congenital; D002648:Child; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D010375:Pedigree; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D013965:Thyroidectomy; D055815:Young Adult
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret