TY - JOUR

T1 - Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients

AU - Bennedbæk, Marc

AU - Rossing, Maria

AU - Rasmussen, Åse K

AU - Gerdes, Anne-Marie

AU - Skytte, Anne-Bine

AU - Jensen, Uffe B

AU - Nielsen, Finn C

AU - Hansen, Thomas v O

PY - 2016

Y1 - 2016

N2 - BACKGROUND: Germline mutations in the succinate dehydrogenase complex genes SDHB, SDHC, and SDHD predispose to pheochromocytomas and paragangliomas. Here, we examine the SDHB, SDHC, and SDHD mutation spectrum in the Danish population by screening of 143 Danish pheochromocytoma and paraganglioma patients.METHODS: Mutational screening was performed by Sanger sequencing or next-generation sequencing. The frequencies of variants of unknown clinical significance, e.g. intronic, missense, and synonymous variants, were determined using the Exome Aggregation Consortium database, while the significance of missense mutations was predicted by in silico and loss of heterozygosity analysis when possible.RESULTS: We report 18 germline variants; nine in SDHB, six in SDHC, and three in SDHD. Of these 18 variants, eight are novel. We classify 12 variants as likely pathogenic/pathogenic, one as likely benign, and five as variants of unknown clinical significance.CONCLUSIONS: Identifying and classifying SDHB, SDHC, and SDHD variants present in the Danish population will augment the growing knowledge on variants in these genes and may support future clinical risk assessments.

AB - BACKGROUND: Germline mutations in the succinate dehydrogenase complex genes SDHB, SDHC, and SDHD predispose to pheochromocytomas and paragangliomas. Here, we examine the SDHB, SDHC, and SDHD mutation spectrum in the Danish population by screening of 143 Danish pheochromocytoma and paraganglioma patients.METHODS: Mutational screening was performed by Sanger sequencing or next-generation sequencing. The frequencies of variants of unknown clinical significance, e.g. intronic, missense, and synonymous variants, were determined using the Exome Aggregation Consortium database, while the significance of missense mutations was predicted by in silico and loss of heterozygosity analysis when possible.RESULTS: We report 18 germline variants; nine in SDHB, six in SDHC, and three in SDHD. Of these 18 variants, eight are novel. We classify 12 variants as likely pathogenic/pathogenic, one as likely benign, and five as variants of unknown clinical significance.CONCLUSIONS: Identifying and classifying SDHB, SDHC, and SDHD variants present in the Danish population will augment the growing knowledge on variants in these genes and may support future clinical risk assessments.

KW - Journal Article

U2 - 10.1186/s13053-016-0053-6

DO - 10.1186/s13053-016-0053-6

M3 - Journal article

C2 - 27279923

VL - 14

SP - 1

EP - 7

JO - Hereditary Cancer in Clinical Practice

JF - Hereditary Cancer in Clinical Practice

SN - 1731-2302

M1 - 13

ER -