Loeys-Dietz syndrome type I and type II: clinical findings and novel mutations in two Italian patients
Loeys-Dietz syndrome type I and type II: clinical findings and novel mutations in two Italian patients
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DOI：
10.1186/1750-1172-4-24
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发表时间：
2009-11-02
影响因子：
3.7
通讯作者：
Colombi, Marina
中科院分区：
文献类型：
--
作者：
Drera, Bruno;Ritelli, Marco;Colombi, Marina
背景资料：Loeys-Dietz综合征（LDS）是一种罕见的常染色体显性遗传疾病，累及皮肤、心血管、颅面和骨骼系统。特别是，LDS患者显示动脉迂曲，伴有广泛的血管动脉瘤和夹层，并且在早期和通常不能预测这些事件的主动脉直径时具有主动脉夹层或破裂的高风险。最近，LDS已被细分为LDS I型（LDSI）和II型（LDSII）的基础上存在或不存在颅面受累，分别。此外，LDSII患者显示至少两个血管Ehlers-Danlos综合征的主要体征。LDS是由转化生长因子（TGF）β受体I（TGFBR 1）和II（TGFBR 2）基因突变引起的。方法：对2例LDS患者的TGFBR 1和TGFBR 2基因外显子和内含子侧翼区进行扩增和序列分析，结果：患者1为男性，表现为巩膜蓝色、腭高弓、悬雍垂双突等畸形体征;骨骼系统受累、关节活动过度、天鹅绒般光滑和半透明的皮肤、主动脉根扩张、颈动脉迂曲和伸长。这些体征与LDSI表型一致。测序分析揭示了新的TGFBR 1 p.Asp351Gly从头突变落在受体的激酶结构域。患者2是一名成年女性，显示升主动脉瘤，手术干预后出现血管并发症。皮肤光滑透明，静脉曲张和腕关节脱位。这些体征与LDSII表型一致。在这个病人和她的女儿，TGFBR 2基因分型披露的蛋白质的激酶结构域的新p.Ile510Ser错义mutation.Conclusion：我们报告两个新的突变TGFBR 1和TGFBR 2基因在两个患者的LDS影响，并表现出显着的表型变异。由于TGFBR相关疾病的临床方法的困难，在血管受累的患者中，有或没有主动脉根部扩张和LDS的主要特征，基因分型是强制性的，以澄清诊断，并评估管理，预后和咨询问题。
Background: Loeys-Dietz syndrome (LDS) is a rare autosomal dominant disorder showing the involvement of cutaneous, cardiovascular, craniofacial, and skeletal systems. In particular, LDS patients show arterial tortuosity with widespread vascular aneurysm and dissection, and have a high risk of aortic dissection or rupture at an early age and at aortic diameters that ordinarily are not predictive of these events. Recently, LDS has been subdivided in LDS type I (LDSI) and type II (LDSII) on the basis of the presence or the absence of cranio-facial involvement, respectively. Furthermore, LDSII patients display at least two of the major signs of vascular Ehlers-Danlos syndrome. LDS is caused by mutations in the transforming growth factor (TGF) beta-receptor I (TGFBR1) and II (TGFBR2) genes. The aim of this study was the clinical and molecular characterization of two LDS patients.Methods: The exons and intronic flanking regions of TGFBR1 and TGFBR2 genes were amplified and sequence analysis was performed.Results: Patient 1 was a boy showing dysmorphic signs, blue sclerae, high-arched palate, bifid uvula; skeletal system involvement, joint hypermobility, velvety and translucent skin, aortic root dilatation, tortuosity and elongation of the carotid arteries. These signs are consistent with an LDSI phenotype. The sequencing analysis disclosed the novel TGFBR1 p.Asp351Gly de novo mutation falling in the kinase domain of the receptor. Patient 2 was an adult woman showing ascending aorta aneurysm, with vascular complications following surgery intervention. Velvety and translucent skin, venous varicosities and wrist dislocation were present. These signs are consistent with an LDSII phenotype. In this patient and in her daughter, TGFBR2 genotyping disclosed in the kinase domain of the protein the novel p.Ile510Ser missense mutation.Conclusion: We report two novel mutations in the TGFBR1 and TGFBR2 genes in two patients affected with LDS and showing marked phenotypic variability. Due to the difficulties in the clinical approach to a TGFBR-related disease, among patients with vascular involvement, with or without aortic root dilatation and LDS cardinal features, genotyping is mandatory to clarify the diagnosis, and to assess the management, prognosis, and counselling issues.