Paraganglioma and pheochromocytoma upon maternal transmission of SDHD mutations

BMC Medical Genetics

Frederik J Hes⁴  Jeroen C Jansen¹  Peter Devilee⁸  Ronald R de Krijger³  Winand NM Dinjens³  Eleonora PM Corssmit⁵  Barbara McGillivray⁶  Esther Korpershoek³  Conny A van der Meer²  Attje S Hoekstra⁷  Jennifer Nuk⁶  Rogier A Oldenburg²  Jean-Pierre Bayley⁷ 

[1] Department of Otorhinolaryngology, Leiden University Medical Center, Leiden, the Netherlands;Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands;Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands;Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands;Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands;Hereditary Cancer Program, BC Cancer Agency, Vancouver, Canada;Department of Human Genetics, Leiden University Medical Center, PZ S-04, Leiden, 2300, RC, the Netherlands;Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands

关键词: Parent-of-origin;    Imprinting;    SDHD;    Pheochromocytoma;    Paraganglioma;   

Others  :  1090456
DOI  :  10.1186/s12881-014-0111-8

 received in 2014-01-14, accepted in 2014-09-24,  发布年份 2014

【 摘 要 】

Background

The SDHD gene encodes a subunit of the mitochondrial tricarboxylic acid cycle enzyme and tumor suppressor, succinate dehydrogenase. Mutations in this gene show a remarkable pattern of parent-of-origin related tumorigenesis, with almost all SDHD-related cases of head and neck paragangliomas and pheochromocytomas attributable to paternally-transmitted mutations.

Methods

Here we explore the underlying molecular basis of three cases of paraganglioma or pheochromocytoma that came to our attention due to apparent maternal transmission of an SDHD mutation. We used DNA analysis of family members to establish the mode of inheritance of each mutation. Genetic and immunohistochemical studies of available tumors were then carried out to confirm SDHD-related tumorigenesis.

Results

We found convincing genetic and immunohistochemical evidence for the maternally-related occurrence of a case of pheochromocytoma, and suggestive evidence in a case of jugular paraganglioma. The third case appears to be a phenocopy, a sporadic paraganglioma in an SDHD mutation carrier with no immunohistochemical or DNA evidence to support a causal link between the mutation and the tumor. Microsatellite analysis in the tumor of patient 1 provided evidence for somatic recombination and loss of the paternal region of chromosome 11 including SDHD and the maternal chromosome including the centromere and the p arm.

Conclusions

Transmission of SDHD mutations via the maternal line can, in rare cases, result in tumorigenesis. Despite this finding, the overwhelming majority of carriers of maternally-transmitted mutations will remain tumor-free throughout life.

【 授权许可】

   
2014 Bayley et al.; licensee BioMed Central Ltd.

【 图 表 】

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