Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas
Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas
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DOI：
10.1136/jmg.39.3.178
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发表时间：
2002-03-01
影响因子：
4
通讯作者：
Rubinstein, WS
中科院分区：
文献类型：
--
作者：
Baysal, BE;Willett-Brozick, JE;Rubinstein, WS
背景：副神经节瘤是一种罕见且高度遗传的神经外胚层来源的肿瘤，通常发生在头颈部区域。线粒体复合物 11 基因 SDHB、SDHC 和 SDHD 中的种系突变会导致遗传性副神经节瘤 (PGL)。方法：我们通过 PCR 扩增和测序评估了一组先前在美国两家耳鼻喉科诊所接受治疗的头颈副神经节瘤患者中 SDHB、SDHC 和 SDHD 基因突变的频率。结果：55 名受试者分为 10 个家庭和 37 个非家族案例。其中五名非家族性病例患有多发性肿瘤。 10 例中有 5 例 (50%) 发现了种系 SDHD 突变。家族性病例和 37 例非家族性病例中的 2 例（接近 5%）。在家族性病例中鉴定出 R38X、P81L、H102L、Q109X 和 L128fsX1 34 突变，在非家族性病例中鉴定出 P81L。两个非家族性病例均患有多个肿瘤。 P81L 和 R38X 突变此前已在其他 PGL 家族中报道过，并且 P81L 被认为是始祖突变。对携带这些突变的不同染色体的等位基因分析没有显示常见疾病单倍型，强烈表明 R38X 和 P81L 是潜在的复发突变。在 10 例家族病例中的 2 例（20%）和 33 例非家族病例中的 1 例（与 3% 相似）中发现了种系 SDHB 突变。在家族病例中鉴定出 PI 31 R 和 M71 fsX80，在 1 例非家族病例中鉴定出 Q59X。该非家族病例有一个孤立的肿瘤。其余4个家系和20个散发病例中未发现SDHC基因突变。结论：SDHD突变是本临床患者系列中头颈部副神经节瘤的主要原因。 SDHD 和 SDHB 突变占家族性病例的 70%，与非家族性病例的 8% 相似。这些结果还表明 SDHD P81L 突变在北方地区具有普遍性。美国是创始人效应和反复突变的结果。
Background: Paragangliomas are rare and highly heritable tumours of neuroectodermal origin that often develop in the head and neck region. Germline mutations in the mitochondrial complex 11 genes, SDHB, SDHC, and SDHD, cause hereditary paraganglioma (PGL).Methods: We assessed the frequency of SDHB, SDHC, and SDHD gene mutations by PCR amplification and sequencing in a set of head and neck paraganglioma patients who were previously managed in two otolaryngology clinics in the USA.Results: Fifty-five subjects were grouped into 10 families and 37 non-familial cases. Five of the nonfamilial cases had multiple tumours. Germline SDHD mutations were identified in five of 10 (50%). familial and two of 37 (similar to5%) non-familial cases. R38X, P81L, H102L, Q109X, and L128fsX1 34 mutations were identified in the familial cases and P81L was identified in the non-familial cases. Both nonfamilial cases had multiple tumours. P81L and R38X mutations have previously been reported in other PGL families and P81L was suggested as a founder mutation. Allelic analyses of different chromosomes carrying these mutations did not show common disease haplotypes, strongly suggesting that R38X and P81L are potentially recurrent mutations. Germline SDHB mutations were identified in two of 10 (20%) familial and one of 33 (similar to3%) non-familial cases. PI 31 R and M71 fsX80 were identified in the familial cases and Q59X was identified in the one non-familial case. The non-familial case had a solitary, tumour. No mutations could be identified in the SDHC gene in the remaining four families and 20 sporadic cases.Conclusions: Mutations in SDHD are the leading cause of head and neck paragangliomas in this clinic patient series. SDHD and SDHB mutations account for 70% of familial cases and similar to8% of non-familial cases. These results also suggest that the commonness of the SDHD P81L mutation in North. America is the result of both a founder effect and recurrent mutations.