Genotype-Phenotype Correlations in Children with HHT.
Genotype-Phenotype Correlations in Children with HHT.
复制标题
DOI：
10.3390/jcm9092714
复制
发表时间：
2020-08-22
影响因子：
3.9
通讯作者：
the Brain Vascular Malformation Consortium HHT Investigator Group
中科院分区：
文献类型：
--
作者：
Kilian A;Latino GA;White AJ;Clark D;Chakinala MM;Ratjen F;McDonald J;Whitehead K;Gossage JR;Lin D;Henderson K;Pollak J;McWilliams JP;Kim H;Lawton MT;Faughnan ME;the Brain Vascular Malformation Consortium HHT Investigator Group
遗传性出血性毛细血管扩张症 (HHT) 是一种罕见的常染色体显性疾病，主要由三个已知基因（ENG、ACVRL1 和 SMAD4）突变引起，其特点是发生血管畸形 (VM)。 HHT 患者可能会出现皮肤粘膜毛细血管扩张，以及中枢神经系统、肺和肝脏的器官动静脉畸形 (AVM)。成人 HHT 的基因型-表型相关性已得到很好的描述。我们的目的是研究儿科 HHT 患者的基因型与表型相关性。收集并分析了参加多中心脑血管畸形联盟 HHT 项目的 205 名儿童的人口统计、临床和遗传数据。卡方检验用于确定表型表现和基因型之间的关联。在 205 名患者（年龄范围：0-18 岁；平均：11 岁）中，ENG 突变与肺 AVM（p < 0.001）和脑 VM（p < 0.001）的存在相关。组合表型（定义为肺 AVM 和脑 VM）的存在也与 ENG 突变相关。胃肠道出血很少见 (4.4%)，但与 SMAD4 基因型相关 (p < 0.001)。我们得出的结论是，儿科 HHT 患者的基因型-表型相关性与成人中描述的相似。具体而言，患有 ENG 突变的儿科患者肺 AVM、脑 VM 和组合表型的患病率更高。
Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (ENG, ACVRL1, and SMAD4), is characterized by the development of vascular malformations (VMs). Patients with HHT may present with mucocutaneous telangiectasia, as well as organ arteriovenous malformations (AVMs) of the central nervous system, lungs, and liver. Genotype–phenotype correlations have been well described in adults with HHT. We aimed to investigate genotype–phenotype correlations among pediatric HHT patients. Demographic, clinical, and genetic data were collected and analyzed in 205 children enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. A chi-square test was used to determine the association between phenotypic presentations and genotype. Among 205 patients (age range: 0–18 years; mean: 11 years), ENG mutation was associated with the presence of pulmonary AVMs (p < 0.001) and brain VM (p < 0.001). The presence of a combined phenotype—defined as both pulmonary AVMs and brain VMs—was also associated with ENG mutation. Gastrointestinal bleeding was rare (4.4%), but was associated with SMAD4 genotype (p < 0.001). We conclude that genotype–phenotype correlations among pediatric HHT patients are similar to those described among adults. Specifically, pediatric patients with ENG mutation have a greater prevalence of pulmonary AVMs, brain VMs, and a combined phenotype.
登录
查看更多内容
影响因子：
3.9
作者：
Maria Mora-Lujan, Jose;Iriarte, Adriana;Riera-Mestre, Antoni
通讯作者：
Riera-Mestre, Antoni
影响因子：
2
作者：
Gallione, Carol;Aylsworth, Arthur S.;Marchuk, Douglas A.
通讯作者：
Marchuk, Douglas A.
影响因子：
4
作者：
Berg, J;Porteous, M;Guttmacher, A
通讯作者：
Guttmacher, A
影响因子：
4
作者：
Gallione, C. J.;Richards, J. A.;Marchuk, D. A.
通讯作者：
Marchuk, D. A.
影响因子：
4
作者：
Letteboer, TGW;Mager, JJ;Westermann, CJJ
通讯作者：
Westermann, CJJ