拓宽新生儿糖尿病患者中致病性 PDX1 变异所导致的表型谱。

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

BMJ Open Diabetes Research & Care Pub Date : 2024-11-14 DOI:10.1136/bmjdrc-2024-004439

Nicola Jeffery, Omar Al Nimri, Jayne A L Houghton, Evgenia Globa, Matthew N Wakeling, Sarah E Flanagan, Andrew T Hattersley, Kashyap Amratlal Patel, Elisa De Franco

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引用次数: 0

摘要

简介：双侧PDX1变体是导致孤立性胰腺发育不全和无胰腺外分泌功能不全的新生儿糖尿病（NDM）的罕见病因，文献中已报道17例：为了确定这种罕见遗传病因导致的表型变异，我们对19例因双倍拷贝致病PDX1变异导致的NDM患者进行了调查：结果：在这 19 人中，8 人（42%）被证实患有外分泌功能不全，需要进行替代治疗。12人（63.2%）具有胰腺外特征，其中8人（42%）的十二指肠和/或肝胆道受到影响。十二指肠发育缺陷与之前在小鼠中进行的 Pdx1 消融研究一致，该研究显示喙十二指肠发育异常：我们的研究结果表明，隐性 PDX1 变体可导致 NDM 的综合征形式，这突出了临床评估 PDX1 变体导致的 NDM 患者胰腺外特征的必要性。

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Widening the phenotypic spectrum caused by pathogenic PDX1 variants in individuals with neonatal diabetes.

Introduction: Biallelic PDX1 variants are a rare cause of isolated pancreatic agenesis and neonatal diabetes (NDM) without exocrine pancreatic insufficiency, with 17 cases reported in the literature.

Research design and methods: To determine the phenotypic variability caused by this rare genetic aetiology, we investigated 19 individuals with NDM resulting from biallelic disease-causing PDX1 variants.

Results: Of the 19 individuals, 8 (42%) were confirmed to have exocrine insufficiency requiring replacement therapy. Twelve individuals (63.2%) had extrapancreatic features, including 8 (42%) with conditions affecting the duodenum and/or hepatobiliary tract. Defects in duodenum development are consistent with previous Pdx1 ablation studies in mice which showed abnormal rostral duodenum development.

Conclusions: Our findings show that recessive PDX1 variants can cause a syndromic form of NDM, highlighting the need for clinical assessment of extrapancreatic features in individuals with NDM caused by PDX1 variants.

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来源期刊

BMJ Open Diabetes Research & Care Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

9.30

自引率

2.40%

发文量

123

审稿时长

18 weeks

期刊介绍： BMJ Open Diabetes Research & Care is an open access journal committed to publishing high-quality, basic and clinical research articles regarding type 1 and type 2 diabetes, and associated complications. Only original content will be accepted, and submissions are subject to rigorous peer review to ensure the publication of high-quality — and evidence-based — original research articles.