背景：Weill-Marchesani综合征（WMS）是一种遗传性结缔组织疾病，在临床特征和遗传病因上具有实质性异质性，因此，定义完整的突变谱对于早期诊断至关重要。在这项研究中,我们报道了由潜伏转化生长因子β结合蛋白2(LTBP2)的新型单倍型突变引起的Weill-Marchesani样综合征(WMS样)向常染色体显性遗传的改变.
方法：从广州招募了来自4代中国家庭的25名成员，其中9人被诊断患有WMS样疾病，九个是健康的，还有7人因为年龄小而临床状况“不确定”。所有成员都接受了详细的身体和眼部检查。全外显子组测序,桑格测序,和实时PCR用于鉴定和验证家族成员的致病突变。
结果：基因测序揭示了与WMS样相关的相同LTBP2染色体上的新型单倍型突变，c.2657C>A/p。T886K在外显子16和外显子25-36的缺失。实时PCR和Sanger测序验证了临床诊断为WMS样的患者的两种突变，和一个“不确定”的孩子。在这些患者中,单倍型突变导致了扁桃体异位，身材矮小和肥胖。
结论：我们的研究表明，WMS样突变可能与具有常染色体显性遗传的单倍型LTBP2突变有关。
BACKGROUND: Weill-Marchesani syndrome (WMS) is a hereditary connective tissue disorder with substantial heterogeneity in clinical features and genetic etiology, so it is essential to define the full mutation spectrum for earlier diagnosis. In this study, we report Weill-Marchesani-like syndrome (WMS-like) change to autosomal dominance inheritance caused by novel haplotypic mutations in latent transforming growth factor beta-binding protein 2 (LTBP2).
METHODS: Twenty-five members from a 4-generation Chinese family were recruited from Guangzhou, of whom nine were diagnosed with WMS-like disease, nine were healthy, and seven were of \"uncertain\" clinical status because of their young age. All members received detailed physical and ocular examinations. Whole-exome sequencing, Sanger sequencing, and real-time PCR were used to identify and verify the causative mutations in family members.
RESULTS: Genetic sequencing revealed novel haplotypic mutations on the same LTBP2 chromosome associated with WMS-like, c. 2657C>A/p.T886K in exon 16 and deletion of exons 25-36. Real-time PCR and Sanger sequencing verified both mutations in patients with clinically diagnosed WMS-like, and in one \"uncertain\" child. In these patients, the haplotypic mutations led to ectopia lentis, short stature, and obesity.
CONCLUSIONS: Our study revealed that WMS-like may be associated with haplotypic LTBP2 mutations with autosomal dominant inheritance.
