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

我提议研究两种影响肝脏的破坏性遗传性疾病：窒息胸廓营养不良(ATD)和婴儿表型腹泻(PDI)。ATD影响身体的许多部位。它的严重程度各不相同，从生命最初几周的死亡到成年后的存活。这种综合征可能会影响纤毛(细胞的一部分)，所以研究ATD也将有助于我们理解纤毛受到影响的其他疾病。患有PDI的儿童在婴儿时期通常会患上肝病，但危及生命的症状是腹泻。通过了解腹泻的原因，可以开发出也可以用于其他腹泻疾病的治疗方法，其他腹泻疾病是世界各地儿童疾病和死亡的主要原因。目的是识别关键基因的特定遗传缺陷(突变)，以便在临床上怀疑这两种疾病中的任何一种时提供强有力的测试。这将有助于对家庭进行咨询，还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治疗这种疾病的特定药物的领域。

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.