title: Common genetic mutations in the start codon of the SDH subunit D gene among Chinese families with familial head and neck paragangliomas.
abstract: Head and neck paragangliomas (HNPGLs) are rare, and frequently associated with germline mutations of the succinate dehydrogenase (SDH) genes, especially for familial cases. The purpose of the study is to explore SDH mutations in Chinese families with familial HNPGLs in Taiwan. Four unrelated families with familial HNPGLs were screened for germline mutations in the SDHB, SDHC and SDHD genes by direct sequencing. One hundred healthy subjects without a diagnosis or family history of HNPGLs were screened as normal controls. Immunohistochemistry with SDHB antibody was performed for a carotid body tumor. Two allele variants were identified, including p.Met1Val (c.1A>G) in the SDHD gene in one family and p.Met1Ile (c.3G>C) in the SDHD gene in the other three families. Both variants are considered pathogenic because of the absence of these variants in 100 normal controls, 100% evolutionary conservation of the p.Met1 residue, co-segregation of the variants with the phenotype of HNPGL in pedigrees, and predicted abolishment of the translation start site. The tumor cells obtained from one proband harboring c.3G>C mis-sense mutation were weak diffuse staining in the cytoplasm of tumors cells. This study demonstrates that two mis-sense mutations at the start codon of the SDHD gene, including p.Met1Val (c.1A>G) and p.Met1Ile (c.3G>C), might be mutation hotspots in Chinese patients with familial HNPGLs.
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Wang
authors.forename: Tseng-Cheng
authors.initials: TC
authors.lastname: Chen
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
authors.forename: Jenq-Yuh
authors.initials: JY
authors.lastname: Ko
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Fei-Yun
authors.initials: FY
authors.lastname: Lo
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Hu
authors.forename: Pei-Lung
authors.initials: PL
authors.lastname: Chen
authors.forename: Chen-Chi
authors.initials: CC
authors.lastname: Wu
authors.forename: Pei-Jen
authors.initials: PJ
authors.lastname: Lou
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D018387:Codon, Initiator / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020125:Mutation, Missense; D010235:Paraganglioma / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*; D013624:Taiwan; D055815:Young Adult
chemical_list: D018387:Codon, Initiator; D013385:Succinate Dehydrogenase