Phenotyping and genotyping of skeletal dysplasias: Evolution of a center and a decade of experience in India
Phenotyping and genotyping of skeletal dysplasias: Evolution of a center and a decade of experience in India
复制标题
DOI：
10.1016/j.bone.2018.10.026
复制
发表时间：
2019-03-01
期刊：
影响因子：
4.1
通讯作者：
Girisha, Katta M.
中科院分区：
文献类型：
--
作者：
Uttarilli, Anusha;Shah, Hitesh;Girisha, Katta M.
遗传异质性、高负担和罕见疾病基因检测的缺乏对印度这些疾病的基因组医疗保健提出了挑战。在这里，我们报告了过去十年在印度一所三级大学医院建立骨骼发育不良基因组评估的经验。通过桑格测序和下一代测序进行研究或临床基因组检测。密切的国家和国际合作有助于表型和基因分型。我们报告了508个家庭（557个受影响的个人）与明确的分子诊断骨骼发育不良。多发性骨发育不全（n = 196）、遗传性炎症/类风湿性骨关节病（n = 114）和骨生成障碍和骨密度降低（n = 58）是最常见的诊断。我们列举了21个基因中48个新变异的队列中的过程，临床诊断和因果变异。我们总结了该中心在临床和突变谱的描述以及新表型和遗传病因学的发现方面的科学贡献。我们的研究说明了骨骼遗传性疾病的基因组检测工具的建立和应用在一个大的队列。我们相信这可以成为其他发展中的遗传中心效仿的模式。
Genetic heterogeneity, high burden and the paucity of genetic testing for rare diseases challenge genomic healthcare for these disorders in India. Here we report our experience over the past decade, of establishing the genomic evaluation of skeletal dysplasia at a tertiary university hospital in India. Research or clinical genomic testing was carried out by Sanger sequencing and next-generation sequencing. Close national and international collaborations aided phenotyping and genotyping. We report 508 families (557 affected individuals) with the definitive molecular diagnosis of skeletal dysplasia. Dysostoses multiplex (n = 196), genetic inflammatory/rheumatoid-like osteoarthropathies (n = 114) and osteogenesis imperfecta and decreased bone density (n = 58) were the most common diagnoses. We enumerate the processes, clinical diagnoses and causal variants in the cohort with 48 novel variants in 21 genes. We summarize scientific contributions of the center to the description of clinical and mutation profiles and discovery of new phenotypes and genetic etiology. Our study illustrates the establishment and application of genomic testing tools for genetic disorders of skeleton in a large cohort. We believe this could be a model to emulate for other developing genetic centers.