Disease Severity in Familial Dysautonomia

Familial Dysautonomia (FD) is a developmental and degenerative genetic disease that manifests in the neural crest cells and peripheral nervous system (PNS). Despite all FD patients having the same mutation in IKBKAP, patients present with varying disease severity, ranging from mild to severe. We used the human pluripotent stem cell technology to recapitulate this varying disease severity in the dish. Further, we found that severe, but not mild patients harbor mutations in candidate modifier genes that may contribute to severe disease presentation.]]>
Fibroblast patient samples were purchased from Coriell Biorepository. The patients were selected based on the accompanying clinical description of symptoms on the Coriell Biorepository website and categorized by us into mild FD or severe FD patient groups.]]>

家族性自主神经功能障碍（Familial Dysautonomia, FD）是一种累及神经嵴细胞与外周神经系统（Peripheral Nervous System, PNS）的发育退行性遗传疾病。尽管所有FD患者均存在IKBKAP基因的同一突变，但患者的疾病严重程度存在显著差异，从轻症到重症不等。本研究借助人多能干细胞技术，在体外培养体系中复现了这种疾病严重程度的异质性。进一步研究发现，重症而非轻症FD患者的候选修饰基因中存在突变，这些突变可能参与重症疾病表型的形成。

患者成纤维细胞样本购自科里尔生物样本库（Coriell Biorepository）。本研究依据科里尔生物样本库官网附带的症状临床描述筛选受试者，并将其分为轻症FD组与重症FD组。