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.
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。