A novel succinate dehydrogenase subunit B germline variant associated with head and neck paraganglioma in a Dutch kindred: a family based study.

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A novel succinate dehydrogenase subunit B germline variant associated with head and neck paraganglioma in a Dutch kindred: a family based study.

Clin Otolaryngol. 2018 Jan 02;:

Authors: de Vos B, Rijken JA, Adank MA, Hoksbergen AWJ, Bayley JP, Leemans CR, Hensen EF

Abstract
OBJECTIVE: In the Netherlands, the majority of hereditary head and neck paragangliomas (HNPGL) are caused by germline variants in the succinate dehydrogenase genes (SDHD, SDHB, SDHAF2). Here, we evaluate a four-generation family linked to a novel SDHB gene variant with the manifestation of a HNPGL.
DESIGN: a family based study.
SETTING: The VU University Medical Center (VUmc) Amsterdam, a tertiary clinic for Otolaryngology and Head and Neck Surgery.
PARTICIPANTS AND MAIN OUTCOME MEASURES: The index patients presented with an embryonic rhabdomyosarcoma and a non-Hodgkin lymphoma. Array-based comparative genomic hybridization (aCGH) analysis and multiplex ligation-dependent probe amplification (MLPA) revealed a novel deletion of exon 1-3 in the SDHB gene, suspected to predispose to paraganglioma (PGL)/pheochromocytoma (PHEO) syndrome type 4. Subsequently, genetic counseling and DNA testing was offered to all family members at risk. Individuals that tested positive for this novel SDHB gene variant were counseled and additional clinical evaluation was offered for the identification of HNPGL and/or PHEO.
RESULTS: The DNA of 18 family members was tested, resulting in the identification of 10 carriers of the exon 1-3 deletion in the SDHB gene. One carrier was diagnosed with a carotid body PGL and serum catecholamine excess, which was surgically excised. Negative SDHB immunostaining of the carotid body tumour confirmed that it was caused by the SDHB variant. The remaining 9 carriers showed no evidence of PGL/PHEO.
CONCLUSION: Deletion of exon 1-3 in the SDHB gene is a novel germline variant associated with the formation of hereditary HNPGL. This article is protected by copyright. All rights reserved.

PMID: 29292578 [PubMed - as supplied by publisher]

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