title: Rare RET Variant p.D707E in a Chinese Pedigree with Hereditary Medullary Thyroid Carcinoma.
abstract: BACKGROUND
  Hereditary medullary thyroid carcinoma (HMTC) is thought to be associated with germline mutations of the RET proto-oncogene.
  
  
  METHODS
  We detected RET proto-oncogene germline mutations from a pedigree with HMTC in the east of China and investigated the characteristics of these mutations in this pedigree and their correlation with HMTC by direct sequencing of all 21 exons in the RET gene of all 46 subjects.
  
  
  CONCLUSIONS
  (1) Thirteen types of RET gene variants were detected in this pedigree. Of these, p.F285S in exon 4, c.854_855CA in exon 4, and p.D707E in exon 11 are reported for the first time in our study. (2) Both linkage disequilibrium analysis and logistic regression analysis showed a significant correlation between the p.D707E variant and HMTC (LOD = 3.69, OR = 4.413, p = 0.000167), indicating that this variant is a risk factor for medullary thyroid carcinoma (MTC). (3) The single-nucleotide polymorphisms (SNP) G691S in exon 11 (rs1799939), S904S in exon 15 (rs1800863), and rs2075912 and rs2565200 in the 3'-untranslated region of the RET proto-oncogene are in complete linkage disequilibrium (D' = 1, r2 = 1); no correlation of these SNP and MTC was observed in this pedigree. (4) No hot-spot mutation of the RET proto-oncogene was detected in this pedigree. We drew the conclusion that the heterozygous nonsynonymous variant p.D707E in the RET proto-oncogene is rare, but it is a risk factor for hereditary MTC.
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, PR China.
authors: Lu
authors: L
authors: Zhang
authors: Xiaoyu
authors: X
authors: Li
authors: Qiyuan
authors: Q
authors: Li
authors: Shengxiang
authors: S
authors: Ge
authors: Mengyuan
authors: M
authors: Chen
authors: Shuizhen
authors: S
authors: Huang
authors: Binbin
authors: B
authors: Chen
authors: Peng
authors: P
authors: Li
authors: Bogang
authors: B
authors: Teng
authors: Jing
authors: J
authors: Xu
authors: Shupeng
authors: S
authors: Zhao
authors: Fengjie
authors: F
authors: Qi
authors: Yongxing
authors: Y
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D044466:Asian People; D018276:Carcinoma, Medullary / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D005091:Exons / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: Hereditary medullary thyroid carcinoma; RET proto-oncogene; Single-nucleotide polymorphism; Variant