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A Family with Co-existing SDHB and SDHD Mutations Causing Hereditary Paraganglioma Syndrome

Deirdre Cilliers, Soo-Mi Park, Kate Sarson, Sue Kenwrick, Helen Simpson, Lindsey Bradley, Fiona Lalloo, Michelle McConachie, Eamonn R Maher

Abstract


Introduction: We report the co-occurrence of a SDHD and a SDHB mutation in a family with hereditary paraganglioma syndrome.  We compare this finding to simultaneous haploinsufficiency of BRCA1 and BRCA2.

Presentation of Case: The 28 year old proband presented as an isolated case in the family with a malignant phaeochromocytoma.  Sequencing and MLPA of SDHD and SDHB were performed.  A SDHD splice site mutation, c.169+5G>A, was identified in the proband, his sister and their father.  In addition, a SDHB exon 1 deletion was identified by MLPA in the proband, his sister and their mother.  Both mutations have been described previously and considered to be pathogenic. An appropriate screening programme was instituted for carrier relatives. 

Conclusions: To our knowledge, this is the first report of two SDH subunit mutations in a single family.  Though there was no family history to suggest inherited disorder, the simultaneous testing of both genes was diagnostic.  The family history is consistent with suggestions that the penetrance of SDHB/SDHD mutations is lower than initially thought.

Keywords


Hereditary paraganglioma syndrome; SDHD; SDHB; Phaeochromocytoma

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References


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