SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, Toronto, ON, Canada.
Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.
Hum Genet. 2023 May;142(5):655-667. doi: 10.1007/s00439-023-02524-6. Epub 2023 Feb 14.
Diarrhoeal disorders in childhood extend beyond the inflammatory bowel diseases. Persistent and severe forms of diarrhoea can occur from birth and are associated with significant morbidity and mortality. These disorders can affect not only the gastrointestinal tract but frequently have extraintestinal manifestations, immunodeficiencies and endocrinopathies. Genomic analysis has advanced our understanding of these conditions and has revealed precision-based treatment options such as potentially curative haematopoietic stem cell transplant. Although many new mutations have been discovered, there is frequently no clear genotype-phenotype correlation. The functional effects of gene mutations can be studied in model systems such as patient-derived organoids. This allows us to further characterise these disorders and advance our understanding of the pathophysiology of the intestinal mucosa. In this review, we will provide an up to date overview of genes involved in diarrhoeal disorders of early onset, particularly focussing on the more recently described gene defects associated with protein loosing enteropathy.
儿童腹泻病不仅包括炎症性肠病。从出生起就可能出现持续性和严重的腹泻，这与较高的发病率和死亡率相关。这些疾病不仅会影响胃肠道，而且常常有肠外表现、免疫缺陷和内分泌疾病。基因组分析使我们对这些疾病有了更深入的了解，并揭示了基于精准医学的治疗选择，如可能治愈的造血干细胞移植。尽管已经发现了许多新的突变，但通常没有明确的基因型-表型相关性。基因突变的功能影响可以在患者来源的类器官等模型系统中进行研究。这使我们能够进一步描述这些疾病，并深入了解肠黏膜的病理生理学。在这篇综述中，我们将提供一个关于早期发病的腹泻病相关基因的最新概述，特别关注与蛋白丢失性肠病相关的最近描述的基因缺陷。
