Germline mutations and genotype–phenotype associations in head and neck paraganglioma patients with negative family history in China

Abstract The aim of this study was to assess the frequency of germline mutations and to explore genotype–phenotype associations in Chinese head and neck paraganglioma (HNPGL) patients without family history. Twenty-six Chinese patients with a diagnosis of HNPGL（14 male and 12 female, respectively）we...

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Bibliographic Details
Published in:European journal of medical genetics 2015-09, Vol.58 (9), p.433-438
Main Authors: Zhu, W.D, Wang, Z.Y, Chai, Y.C, Wang, X.W, Chen, D.Y, Wu, H
Format: Article
Language:English
Subjects:
Adult
Aged
Amino Acid Sequence
Asian Continental Ancestry Group - genetics
China
Female
Follow-Up Studies
Genetic analysis
Genetic Association Studies
Genetic Testing
Germ-Line Mutation
Germline mutation
Head and Neck Neoplasms - diagnosis
Head and Neck Neoplasms - genetics
Head and neck paraganglioma (HNPGL)
Heterozygote
Humans
Male
Medical Education
Middle Aged
Molecular Sequence Data
Multiplex ligation-dependent probe amplification (MLPA)
Mutation, Missense
Paraganglioma - diagnosis
Paraganglioma - genetics
SDHAF2
SDHB
SDHD
Succinate Dehydrogenase - genetics
Succinate Dehydrogenase - metabolism
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Summary:Abstract The aim of this study was to assess the frequency of germline mutations and to explore genotype–phenotype associations in Chinese head and neck paraganglioma (HNPGL) patients without family history. Twenty-six Chinese patients with a diagnosis of HNPGL（14 male and 12 female, respectively）were recruited, who were followed up from 2000 to 2012. Genomic DNA was obtained from resected tumor tissues and peripheral blood samples. Seven genes, Succinate dehydrogenase complex A,B,C,D (SDHA, SDHB, SDHC, SDHD ), succinate dehydrogenase complex assembly factor 2 (SDHAF2 ), TMEM127 (transmembrane protein 127) and VHL (Von Hippel-Lindau), were screened by direct sequencing and multiplex ligation-dependent probe amplification (MLPA) was performed to search for potential large deletions or duplications of SDHB, SDHC, SDHD, SDHAF1 and SDHAF2 . The total frequency of germline mutations was 30.8% (8/26), including 5 cases with missense mutation p.Met1Ile in SDHD , 1 case with missense mutation p.Tyr216Cys in SDHB , and 1 case with a novel truncation mutation p.Gln44Ter in SDHAF2 . MLPA showed one patient with malignant HNPGL had heterozygous deletions of exon1, 2, 3, 7 and 8 in SDHB . Mutations in SDHD were the leading cause of HNPGL in this study. Mutation carriers were younger than non-mutation carriers ( p  
ISSN:1769-7212
1878-0849
DOI:10.1016/j.ejmg.2015.05.008