Hereditary paraganglioma due to the SDHD M1I mutation in a second Chinese family: a founder effect?
OBJECTIVE
Hereditary paraganglioma is a rare condition that is inherited in an autosomal-dominant fashion. Four distinct loci have been associated with hereditary paraganglioma, including the SDHD, SDHC, and SDHB genes and a locus at 11q13. The SDHD, SDHC, and SDHB genes code for subunits of succinate dehydrogenase, which forms part of the mitochondrial respiratory chain. SDHD mutations are widely distributed along the gene with no apparent hot spots, although a founder effect has been described in the Dutch population.


METHODS
Following a prior report of the SDHD M1I mutation in an Australian Chinese family, a second Chinese family with the same mutation is reported. The proband developed bilateral head and neck paragangliomas at age 34 years and a functioning adrenal pheochromocytoma and two extra-adrenal abdominal paragangliomas 7 years later. His brother had unilateral head and neck paraganglioma at age 39 years. Given the multicentricity of the proband's tumor and the familial clustering of paragangliomas, a clinical diagnosis of hereditary paraganglioma was made, and the proband was tested for a mutation in the SDHD gene.


RESULTS
The proband was found to be heterozygous for the SDHD MII mutation that removes the start codon, and his brother subsequently tested positive for the same mutation. The family is not related to the Australian Chinese family.


CONCLUSIONS
The finding suggests the possibility of a founder effect in the Chinese population and warrants further investigation.
Lee
Soo-Chin
SC
Department of Hematology-Oncology, National University Hospital, Singapore. LeeSC@nuh.com.sg
Chionh
Siok-Bee
SB
Chong
Siew-Meng
SM
Taschner
Peter E M
PE
D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D002344:Carotid Body / Q000473:pathology; D002681:China / Q000208:ethnology; D002869:Chromosome Aberrations; D003062:Codon; D004252:DNA Mutational Analysis; D042963:Electron Transport Complex II; D005260:Female; D018703:Founder Effect; D005799:Genes, Dominant / Q000235:genetics; D006580:Genetic Carrier Screening; D005925:Glomus Jugulare Tumor / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics*; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D010088:Oxidoreductases / Q000235:genetics*; D010235:Paraganglioma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010673:Pheochromocytoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D021122:Protein Subunits; D012846:Singapore; D013385:Succinate Dehydrogenase / Q000235:genetics*
D003062:Codon; D007506:Iron-Sulfur Proteins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D021122:Protein Subunits; C108096:SDHC protein, human; D010088:Oxidoreductases; D042963:Electron Transport Complex II; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase