Aleixo多伦多儿童医院 M. Muise团队在研究方面取得了进展。最近的研究提出了先天性腹泻和肠病的遗传结构。2025年4月3日，新英格兰医学杂志上发表了相关论文。

背景:新一代测序技术使精确的治疗方案成为可能，改善了患有罕见疾病的儿童的生活。先天性腹泻和肠道疾病(CODEs)与高发病率和死亡率有关。虽然这些疾病的治疗在一定程度上是一体化的，但基因诊断的新型靶向治疗包括特定的饮食、药物治疗和手术干预。

方法:研究小组的研究人员对疑似单基因先天性腹泻患者的外显子组或基因组进行了分析。利用细胞和斑马鱼模型，研究小组测试了新型基因突变的影响。

结果:在研究小组129例疑似单基因先天性腹泻的婴儿先证病例系列中，研究小组在62例(48%)婴儿中发现了因果变异，其中包括新始祖NEUROG3变异。利用细胞和斑马鱼模型，该团队还发现了GRWD11的三个与CODEs相关的新基因、MON1A和MYO1AA，并且进行了功能表征。

研究结果表明，该研究小组已在大量病例系列病人中表征了CODE疾病的一般遗传结构，并对与CODE相关的三种新基因进行了鉴定。

附：英文原文

Title: The Genetic Architecture of Congenital Diarrhea and Enteropathy

Author: Zeenat Gaibee, Neil Warner, Katlynn Bugda Gwilt, Wenjuan Li, Rei Guan, Michael Yourshaw, Ryder Whittaker Hawkins, Christiane Zorbas, Jonathan St.-Germain, Mahdi Tabatabaie, Suli Mao, Vered Pinsk, Baruch Yerushalmi, Lee-kai Wang, Stanley F. Nelson, Laura Wozniak, Dror S. Shouval, Manar Matar, Amit Assa, Nathaniel Frost, Lissette Jimenez, Sari Acra, Thomas Walters, Stephen Mouat, Michael Li, Denis L.J. Lafontaine, Matthew Tyska, Brian Raught, Yaron Avitzur, Wayne I. Lencer, James R. Goldenring, Martín G. Martín, Jay R. Thiagarajah, Aleixo M. Muise

Issue&Volume: 2025-04-03

Abstract: BACKGROUND

Next-generation sequencing has enabled precision therapeutic approaches that have improved the lives of children with rare diseases. Congenital diarrhea and enteropathies (CODEs) are associated with high morbidity and mortality. Although treatment of these disorders is largely supportive, emerging targeted therapies based on genetic diagnoses include specific diets, pharmacologic treatments, and surgical interventions.

METHODS

We analyzed the exomes or genomes of infants with suspected monogenic congenital diarrheal disorders. Using cell and zebrafish models, we tested the effects of variants in newly implicated genes.

RESULTS

In our case series of 129 infant probands with suspected monogenic congenital diarrheal disorders, we identified causal variants, including a new founder NEUROG3 variant, in 62 infants (48%). Using cell and zebrafish models, we also uncovered and functionally characterized three novel genes associated with CODEs: GRWD1, MYO1A, and MON1A.

CONCLUSIONS

We have characterized the broad genetic architecture of CODE disorders in a large case series of patients and identified three novel genes associated with CODEs.