Sporadic paraganglioma caused by de novo SDHB mutations in a 6-year-old girl
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Germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene (SDHB) cause susceptibility to paragangliomas and pheochromocytomas; however, it is exceedingly rare in childhood and especially in sporadic cases. We report the first Japanese pediatric case of paraganglioma with a de novo mutation in the SDHB gene. A 6-year-old girl with convulsions and hypertension was found to have a paravertebral abdominal tumor. Urinary and blood examinations revealed markedly elevated levels of norepinephrine. Following treatment for hypertension, the tumor was removed completely and histological findings were consistent with paraganglioma. Immunohistochemistry studies demonstrated the absence of SDHB protein expression, indicating an underlying SDH mutation with high probability. Germline mutation analysis of the SDHB gene revealed a heterozygous splice site mutation in intron 4 (C.423 + 1G > A). Subsequently, a second somatic genetic change was confirmed by multiplex ligation-dependent probe amplification (MLPA) analysis, showing that deletion of the wild-type allele resulted in loss of function of SDHB. No germline mutations in SDHB were detected in her parents.
What is Known
• Most sporadic cases of paraganglioma with SDHB mutations occur between adolescence and adulthood.
• Screening methods for carriers of SDHB mutations assessing recurrence and detecting developing metastases are yet to be standardized.
What is New
• The current case of an extra-adrenal paraganglioma with a de novo SDHB mutation had an onset at 6 years.
• We suggest much closer periodical observation for these high-risk children.
KeywordsParaganglioma Childhood Succinate dehydrogenase complex subunit B Screening Multiplex ligation-dependent probe amplification Loss of heterozygosity
Loss of heterozygosity
Multiplex ligation-dependent probe amplification
Succinate dehydrogenase complex subunit B
We are grateful to Hirohito Shima and Keiko Matsubara, Department of Molecular Endocrinology, National Research Institute for Child Health and Development, for performing microsatellite analysis to confirm the paternity.
Conflict of interest
The authors declare that they have no competing interests.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethics committee of the Medical Faculty of Miyazaki University, Miyazaki, Japan, and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
HI, ET, and TK clinically managed the patient. HI wrote the manuscript under HN’s supervision. KM and TS were responsible for the genetic analysis. NK was responsible for the immunohistochemistry study of SDHB and wrote the manuscript. KT and HM contributed to genetic analysis and interpretation. KM, TS, NK, KT, HM, and HN critically reviewed the manuscript. All the authors approved the final copy of the manuscript.
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