Martinez-Delgado Beatriz, Barrero Maria J
Molecular Genetics Unit, Institute of Rare Diseases Research (IIER), Spanish National Institute of Health Carlos III (ISCIII), 28220 Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras, CIBERER U758, 28029 Madrid, Spain.
Epigenomes. 2022 Jul 27;6(3):21. doi: 10.3390/epigenomes6030021.
Rare diseases affect more than 300 million people worldwide. Diagnosing rare diseases is a major challenge as they have different causes and etiologies. Careful assessment of clinical symptoms often leads to the testing of the most common genetic alterations that could explain the disease. Patients with negative results for these tests frequently undergo whole exome or genome sequencing, leading to the identification of the molecular cause of the disease in 50% of patients at best. Therefore, a significant proportion of patients remain undiagnosed after sequencing their genome. Recently, approaches based on functional aspects of the genome, including transcriptomics and epigenomics, are beginning to emerge. Here, we will review these approaches, including studies that have successfully provided diagnoses for complex undiagnosed cases.
罕见病影响着全球超过3亿人。诊断罕见病是一项重大挑战，因为它们有着不同的病因。仔细评估临床症状往往会促使对最常见的可能解释该疾病的基因改变进行检测。这些检测结果为阴性的患者常常会接受全外显子组或基因组测序，而这最多只能在50%的患者中确定疾病的分子病因。因此，相当一部分患者在对其基因组进行测序后仍未得到诊断。最近，基于基因组功能方面的方法，包括转录组学和表观基因组学，开始出现。在此，我们将对这些方法进行综述，包括那些已成功为复杂的未确诊病例提供诊断的研究。
