Case report of a man with multiple paragangliomas and pathogenic germline variants in both NF1 and SDHD
| Autor: | Mufaddal T. Moonim, Shazia K. Afridi, Louise Izatt, Prodromos Chatzikyriakou, Rupert Obholzer, Ann Sandison, Rebecca J. Oakey, Philip Touska |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Proband
Adult Male congenital hereditary and neonatal diseases and abnormalities Cancer Research Pathology medicine.medical_specialty Genetic counseling Disease Biology Germline Pheochromocytoma Paraganglioma 03 medical and health sciences 0302 clinical medicine Genetics medicine Humans Molecular Biology Exome sequencing Germ-Line Mutation Neurofibromin 1 Base Sequence medicine.disease Pedigree Succinate Dehydrogenase Head and Neck Neoplasms 030220 oncology & carcinogenesis Female SDHD |
| Zdroj: | Cancer genetics. |
| ISSN: | 2210-7762 |
| Popis: | We report a novel case of multiple paragangliomas in a patient who was identified with pathogenic variants in both NF1 and SDHD genes. The proband is a man with known familial NF1 disease, diagnosed clinically in childhood. Multiple head and neck paragangliomas (HNPGL) were found during investigations for acute left sided neurological symptoms, in the region of his known plexiform neurofibroma. He was referred for genetic counselling. He underwent surgery to remove a left carotid body tumor (CBT). A pheochromocytoma and paraganglioma gene panel was tested. Blood and HNPGL tumor DNA were analyzed by whole exome sequencing. In addition to the NF1 truncating variant c.5107delA, p.(Ser1703AlafsTer7), the SDHD truncating pathogenic variant c.3G > A, p.(Met1?) was found. Tumor sequencing showed no LOH of SDHD or NF1, but monoallelic loss of 11p15 and 11q12.2-q12.3 was observed. Co-occurrence of pathogenic variants in multiple cancer susceptibility genes is rare but possible, identified by the increased use of panel testing. This is the first description of a patient presenting with NF1 and SDHD dual pathology, with HNPGL development due to SDHD. This case illustrates the central role of genetic sequencing in PPGLs and the strong genotype-phenotype correlations of different genes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect