Glueck Charles J, Tracy Trent, Wang Ping
Cholesterol Center, Jewish Hospital, Cincinnati, OH 45229, USA.
J Pediatr Orthop. 2007 Oct-Nov;27(7):834-7. doi: 10.1097/BPO.0b013e31815584bf.
In a 4-generation kindred identified through a 12-year-old female proband with Legg-Calve-Perthes Disease (LCPD) who was found to be heterozygous for the G1691A factor V Leiden mutation (FV), our specific aim was to assess associations of FV with LCPD and with venous and arterial thrombotic events. Despite lethal thromboembolism in 3 family members at ages 21, 35, and 38, retinal artery thrombosis, and deep venous thrombosis, no family members had previously been studied for the FV mutation until kindred screening-genetic counseling was prompted by the discovery of the FV mutation in a child proband with LCPD.
In a 4-generation kindred identified through a 12-year-old female proband with LCPD and found to be heterozygous for the FV mutation, we assessed the FV genotype and its association with thromboembolism in 14 of 16 living first- and second-degree relatives.
There was 3-generation vertical and horizontal transmission of heterozygosity for the FV mutation. Of 14 living first- and second-degree relatives, 10 were heterozygous for the FV mutation, including the proband's sister, mother, and maternal grandmother. Of the 14 living relatives, 2 had thrombotic events (retinal artery thrombosis and deep venous thrombosis of the leg). The proband's maternal great-grandfather had a lethal pulmonary embolus at age 35, as did her maternal great aunt at age 38, and a female third cousin at age 21.
In a large kindred identified by a child with LCPD who was found to have the FV mutation, FV heterozygosity was found in 3 generations of previously undiagnosed family members and was associated with venous and arterial thrombosis throughout the kindred. We suggest that FV mutation be studied in children with LCPD facilitate diagnosis and genetic counseling for thrombophilia in their parents, siblings, and other kindred members, and because the proband LCPD child with the FV mutation is at increased risk for other thromboembolic abnormalities as an adult.
在一个通过一名12岁患有Legg-Calve-Perthes病（LCPD）的女性先证者确定的四代家族中，发现该先证者为G1691A因子V Leiden突变（FV）杂合子，我们的具体目标是评估FV与LCPD以及静脉和动脉血栓形成事件之间的关联。尽管有3名家族成员分别在21岁、35岁和38岁时发生致命性血栓栓塞、视网膜动脉血栓形成和深静脉血栓形成，但在一名患有LCPD的儿童先证者中发现FV突变并促使进行家族筛查 - 遗传咨询之前，此前没有家族成员接受过FV突变研究。
在一个通过一名患有LCPD的12岁女性先证者确定且发现为FV突变杂合子的四代家族中，我们评估了16名在世的一级和二级亲属中14人的FV基因型及其与血栓栓塞的关联。
FV突变杂合性存在三代垂直和水平传递。在14名在世的一级和二级亲属中，10人为FV突变杂合子，包括先证者的姐妹、母亲和外祖母。在这14名在世亲属中，2人发生了血栓形成事件（视网膜动脉血栓形成和腿部深静脉血栓形成）。先证者的外曾祖父在35岁时发生致命性肺栓塞，她的外曾姨在38岁时也发生了同样情况，一名女性第三代堂妹在21岁时发生了致命性肺栓塞。
在一个由患有LCPD且发现有FV突变的儿童确定的大家族中，在三代此前未被诊断的家族成员中发现了FV杂合性，并且与整个家族中的静脉和动脉血栓形成相关。我们建议对患有LCPD的儿童进行FV突变研究，以便为其父母、兄弟姐妹和其他家族成员的血栓形成倾向进行诊断和遗传咨询，并且因为患有FV突变的先证者LCPD儿童成年后发生其他血栓栓塞异常的风险增加。
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