Phosphomannomutase 2 (PMM2) variants leading to hyperinsulinism-polycystic kidney disease are associated with early-onset inflammatory bowel disease and gastric antral foveolar hyperplasia.
Phosphomannomutase 2 (PMM2) variants leading to hyperinsulinism-polycystic kidney disease are associated with early-onset inflammatory bowel disease and gastric antral foveolar hyperplasia.
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DOI：
10.1007/s00439-023-02523-7
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发表时间：
2023-05
期刊：
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
磷酸腺苷转氨酶2 （PMM2）缺乏导致先天性糖基化障碍（PMM2- cdg），但与炎症性肠病（IBD）没有公认的关联。高胰岛素血症和常染色体隐性多囊肾病（HIPKD）的独特临床综合征出现在PMM2启动子的特定变异的背景下，无论是纯合子，还是与有害的PMM2变异的复合杂合。在这里，我们描述了3例PMM2-HIPKD患者的IBD发展，分别在0岁、6岁和10岁发病。在每个病例中，肠道炎症与胃窦小窝增生的异常发现相吻合。IBD疾病在发病时的严重程度不同，但通过常规和一线生物治疗方法得到了很好的控制。PMM2-HIPKD-IBD疾病表现的器官水平模式可能反映了肝细胞核因子4 α (HNF4A)顺式调节控制的缺失。对已发表的转录组学数据的分析表明，IBD最有可能是由于对上皮细胞功能的影响而产生的。我们确定了PMM2的特定变异模式，作为早发性IBD与独特胃病理的新关联。在线版本包含补充资料，下载地址：10.1007/s00439-023-02523-7。
Phosphomannomutase 2 (PMM2) deficiency causes Congenital Disorder of Glycosylation (PMM2-CDG), but does not have a recognised association with Inflammatory Bowel Disease (IBD). A distinct clinical syndrome of hyperinsulinism and autosomal recessive polycystic kidney disease (HIPKD) arises in the context of a specific variant in the PMM2 promotor, either in homozygosity, or compound heterozygous with a deleterious PMM2 variant. Here, we describe the development of IBD in three patients with PMM2-HIPKD, with onset of IBD at 0, 6, and 10 years of age. In each case, intestinal inflammation coincided with the unusual finding of gastric antral foveolar hyperplasia. IBD disease was of variable severity at onset but well controlled with conventional and first-line biologic treatment approaches. The organ-level pattern of disease manifestations in PMM2-HIPKD-IBD may reflect a loss of cis-acting regulatory control by hepatocyte nuclear factor 4 alpha (HNF4A). Analysis of published transcriptomic data suggests that IBD most likely arises due to an impact on epithelial cellular function. We identify a specific pattern of variation in PMM2 as a novel association of early-onset IBD with distinctive gastric pathology. The online version contains supplementary material available at 10.1007/s00439-023-02523-7.
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影响因子：
9.8
作者：
Matthijs, G;Schollen, E;Jaeken, J
通讯作者：
Jaeken, J
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影响因子：
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作者：
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影响因子：
64.8
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--
DOI：
10.1016/j.jcmgh.2021.07.001
发表时间：
2021
影响因子：
7.2
作者：
Al-Shaibi AA;Abdel-Motal UM;Hubrack SZ;Bullock AN;Al-Marri AA;Agrebi N;Al-Subaiey AA;Ibrahim NA;Charles AK;COLORS in IBD-Qatar Study Group;Elawad M;Uhlig HH;Lo B
通讯作者：
Lo B