醫學遺傳學及基因體學每月研討會 ─ Whole Exome Sequencing for Pediatric Undiagnosed Diseases
李妮鍾 助理教授 (臺大醫院基因醫學部主治醫師)
Genetics is now an important cause of childhood diseases, including congenital malformation and inborn errors of metabolism. Although the incidence of each disease is low, adding together those more than 4,000 known genetic diseases, the combined incidence of all genetic diseases is quite high. Diagnosis of genetic disease may start from the recognition of specific phenotype syndromes, unique radiographic features, pathologic histological findings, or characteristic metabolic compounds. Confirmation of genetic diseases then depends on the discovery of disease causing gene mutations. Sequencing of one gene is not difficult. However, clinical and laboratory finding may not be able to define a specific disease, and several candidate genes need to be sequenced. Moreover, we now know a specific phenotype (traditionally defined as a disease) can be caused by several or many genes. Therefore, the number of genes that need to be sequenced for one phenotype can be large, for example, there are around 30 genes responsible for hereditary non-syndromic hearing loss, and more than 200 genes for mitochondrial diseases. After the development of next generation sequencing (NGS) technology, targeted genes of specific phenotype can be sequencing as disease panel. In the past few years, we have employed these technologies to pediatric patients suspected to have specific phenotype. However, the positive rate is low. Recently, whole-exome sequencing had been applied to clinical practice in pediatric patients with unrecognized phenotype with better yields. In this talk, I will review the current genetic testing strategies and share experiences of results on the diagnosis of genetic disease.