Telomere Shortening Is Associated with Genetic Anticipation in Chinese Von Hippel-Lindau Disease Families
Telomere Shortening Is Associated with Genetic Anticipation in Chinese Von Hippel-Lindau Disease Families
复制标题
端粒缩短与中国 Von Hippel-Lindau 病家族的遗传预期相关。
DOI：
10.1158/0008-5472.can-14-0024
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发表时间：
2014-07-15
期刊：
影响因子：
11.2
通讯作者：
Gong, Kan
中科院分区：
文献类型：
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作者：
Ning, Xiang-hui;Zhang, Ning;Gong, Kan
Von Hippel-Lindau（VHL）病是一种罕见的常染色体显性遗传癌症综合征。在一些遗传性癌症综合征中，有一种被称为遗传预期的现象被证明与端粒缩短有关。由于这一现象在VHL疾病的研究一直相对较少，我们调查了18个中国VHL疾病的家庭预期。我们从18个VHL疾病家族中招募了34对父母-子女患者（57例患者）。发病年龄定义为VHL疾病的任何症状或体征首次出现时的年龄。对发病年龄的预测采用配对t检验及HV和RY 2两种特殊检验。对29例患者和325例健康对照者的外周血白细胞端粒相对长度进行了测定。在34对亲子中，有31对儿童的发病年龄小于父母。在8个VHL家系的10对亲子对中，第一代患者发病年龄较大，年龄校正的相对端粒长度较长，而下一代患者发病年龄较小，年龄校正的相对端粒长度较短（P < 0.001）。此外，29例VHL患者的相对端粒长度比正常对照组短（P = 0.003）。这种预期可能与VHL患者连续几代端粒长度缩短有关。这些结果提示VHL病家系中存在着预期遗传现象，对VHL病家系的遗传咨询和进一步了解VHL病的发病机制有一定的帮助。
Von Hippel-Lindau (VHL) disease is a rare autosomal dominant cancer syndrome. A phenomenon known as genetic anticipation has been documented in some hereditary cancer syndromes, where it was proved to relate to telomere shortening. Because studies of this phenomenon in VHL disease have been relatively scarce, we investigated anticipation in 18 Chinese VHL disease families. We recruited 34 parent-child patient pairs (57 patients) from 18 families with VHL disease. Onset age was defined as the age when any symptom or sign of VHL disease first appeared. Anticipation of onset age was analyzed by paired t test and the other two special tests (HV and RY2). Relative telomere length of peripheral leukocytes was measured in 29 patients and 325 healthy controls. Onset age was younger in child than in parent in 31 of the 34 parent-child pairs. Patients in the first generation had older onset age with longer age-adjusted relative telomere length, and those in the next generation had younger onset age with shorter age-adjusted relative telomere length (P < 0.001) in the 10 parent-child pairs from eight families with VHL disease. In addition, relative telomere length was shorter in the 29 patients with VHL disease than in the normal controls (P = 0.003). The anticipation may relate to the shortening of telomere length in patients with VHL in successive generations. These findings indicate that anticipation is present in families with VHL disease and may be helpful for genetic counseling for families with VHL disease families and for further understanding the pathogenesis of VHL disease.