The molecular genetics of inherited liver disease: asphyxiating thoracic dystrophy and phenotypic diarrhoea of infancy

我建议研究影响肝脏的两种毁灭性的遗传性疾病：窒息性胸营养不良（ATD）和婴儿期表型腹泻（PDI）。ATD会影响身体的许多部位。它的严重程度各不相同，从生命的最初几周死亡到存活到成年。该综合征可能会影响纤毛（细胞的一部分），因此研究ATD也将有助于我们了解纤毛受影响的其他疾病。患有PDI的儿童通常会在婴儿时期患上肝脏疾病，但危及生命的症状是腹泻。通过了解腹泻的病因，可以开发治疗方法，这些治疗方法也可用于其他腹泻疾病，腹泻是全世界儿童疾病和死亡的主要原因。其目的是确定关键基因中的特定遗传缺陷（突变），从而在临床理由怀疑这两种情况中的任何一种时提供可靠的测试。这将有助于为家庭提供咨询，也将提供产前诊断测试。研究疾病基因如何影响细胞也将确定特定药物治疗疾病的领域。

I am proposing to study two devastating inherited conditions affecting the liver: asphyxiating thoracic dystrophy (ATD) and phenotypic diarrhoea of infancy (PDI). ATD affects many parts of the body. It varies in severity, from death in the first weeks of life to survival into adulthood. The syndrome may affect cilia (part of a cell), so studying ATD will also help our understanding of other disorders where cilia are affected. With PDI, child often develop liver disease as babies, but the life-threatening symptom is diarrhoea. By understanding the cause of diarrhoea, therapies can be developed which could also be used in other diarrhoeal conditions, a leading cause of disease and death in children worldwide.The aim is to identify the specific genetic defects (mutations) in key genes, so providing a robust test when either of the conditions are suspected on clinical grounds. This will help in counselling families and will also provide a prenatal diagnostic test. Researching how the disease gene affects the cell will also identify areas for specific medicines to treat the conditions.