嗜鉻細胞瘤和/或副神經節瘤的基因檢測與遺傳諮詢

Abstract

嗜鉻細胞瘤（Pheochromocytoma）和副神經節瘤（Paraganglioma）是分別起源於腎上腺髓質或腎上腺外交感神經的腫瘤，前者主要合成和分泌兒茶酚胺（Catecholamine），如去甲腎上腺素（norepinephrine）、腎上腺素（epinephrine）、多巴胺（Dopamine），後者的大量釋放引起症狀，進而引起患者會出現有高血壓、陣發性頭痛、出汗、心悸等臨床症狀，並造成心、腦、腎等嚴重併發症。 本論文因收集嗜鉻細胞瘤/副神經節瘤患者的DNA進行基因檢測的時間為2010年，當時只知這兩種疾病的基因突變有關的基因為RET、VHL、SDHB、SDHC、SDHD，而至今已知與其疾病的基因突有關的基因增加為SDHA、NF1、KIF1B、MAX、TMEM127，共10種基因相關，目前嗜鉻細胞瘤/副神經節瘤患者可由臨床症狀去進行基因檢測方法，只針對7位受試者進行5個基因檢測，其中有找到突變點位為5/7（佔67%），另外沒有找到突變點位為2/7（佔33%）；在7名患者中，有5位的基因檢測找到基因點位，且這5位患者皆有臨床上發現頸部頸部或下巴有腫塊的症狀，有1位發現在SDHB基因突變和有4位發現在SDHD基因突變。 這種在基因型和表現型之間，有密切關聯的腫瘤症候群，希望能夠建立分子生物基因檢測和遺傳諮詢的模式，以便於已經出現症狀的患者和家族中可能有其他潛在潛在的患者患者，提供必要的基因檢測、給予適當的醫療，在遺傳諮詢同時，可再教育患者及家屬嗜鉻細胞瘤和/或副神經節瘤發生的原因，以及對此疾病有正確的認識。

Pheochromocytoma and paraganglioma are tumors that originate from adrenal medulla or adrenal gonadal ganglion. The mainly synthesizing and secreting large amounts of catecholamine, such as norepinephrine, epinephrine. For these two diseases, main symptoms are hypertension, paroxysmal headache, sweating, palpitations and other clinical symptoms, and cause heart, brain, kidney and other serious complications. In this thesis, we enrolled the patients with pheochromocyroma/ paraganglioma in 2010, and extracted their DNA form PBMC (peripheral blood mononuclear cell). At that time, we only know these two diseases related to RET, VHL, SDHB, SDHC, SDHD. However, with the progress of genetic medicine, we found that SDHA, NF1, KIF1B, MAX, and TMEM127 were also related to these two diseases. At present, pheochromocytoma / paraganglioma patients can be carried out by clinical symptoms of genetic testing methods. We only tested these 7 patients with previous 5 genes, and found a detection rate with 67% (5/7); the other two patients didn’t find any variants in these 5 genes. There are five genes that detect gene mutation in 7 subjects, and they all have clinical symptoms. We found one mutation in the SDHB gene and was found in the SDHD gene mutation with 4 subjects. Between the genotypes and phenotypes, there are close associated tumor syndromes. I hope to establish a molecular gene detection and a genetic counseling model. Therefore, we can provide necessary genetic testing and proper medical care for those patients and their families. At the same time, we can educate patients and their families about the causes of pheochromocytoma / paraganglioma, and have a correct understanding of the disease.