Low penetrance of paraganglioma and pheochromocytoma in an extended kindred with a germline SDHB exon 3 deletion.

Autor: Rijken JA; Department of Otolaryngology - Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands., Niemeijer ND; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands., Corssmit EP; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands., Jonker MA; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands., Leemans CR; Department of Otolaryngology - Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands., Menko FH; Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.; Department of Clinical Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands., Hensen EF; Department of Otolaryngology - Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2016 Jan; Vol. 89 (1), pp. 128-32. Date of Electronic Publication: 2015 Apr 27.
DOI: 10.1111/cge.12591
Abstrakt: In the Netherlands, the majority of hereditary paragangliomas (PGL) is caused by SDHD, SDHB and SDHAF2 mutations. Founder mutations in SDHD are particularly prevalent, but several SDHB founder mutations have also been described. Here, we describe an extended PGL family with a Dutch founder mutation in SDHB, c.201-4429_287-933del. The proband presented with apparently sporadic head and neck paraganglioma at advanced age. Subsequently, evaluation of the family identified several unaffected mutation carriers, asymptomatic and symptomatic PGL patients, and patients presenting with early-onset malignant pheochromocytoma. The calculated penetrance of the SDHB mutation in this kindred is lower than the risk suggested for SDHB mutations in the literature. This may represent a characteristic of this particular SDHB mutation, but may also be a reflection of the inclusion of relatively large numbers of asymptomatic mutation carriers in this family and adequate statistical correction for ascertainment bias. The low penetrance of SDHB mutations may obscure the hereditary nature of SDHB-linked disease and is important in the counseling of SDHB-linked patients. Risk estimates should preferably be based on the specific mutation involved.
(© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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