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Hereditary Paraganglioma Due to the SDHD M1I Mutation in a Second Chinese Family: A Founder Effect?
Author(s) -
Lee SooChin,
Chionh SiokBee,
Chong SiewMeng,
Taschner Peter E. M.
Publication year - 2003
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200306000-00026
Subject(s) - sdhd , sdhb , paraganglioma , proband , genetics , population , pheochromocytoma , medicine , mutation , biology , germline mutation , gene , pathology , environmental health
Objectives/Hypothesis 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. Conclusion The finding suggests the possibility of a founder effect in the Chinese population and warrants further investigation.