Laboratoire de Génétique et Biologie Moléculaires, Hôpital Cochin, APHP. Centre-Université de Paris, France.
Service de Pancréatologie-Gastroentérologie, Pôle des Maladies de l'Appareil Digestif, Université Denis Diderot, Hôpital Beaujon, APHP, DHU UNITY, Clichy, France; Centre de Référence des Maladies Rares du Pancréas, PAncreaticRaresDISeases (PaRaDis), France.
Pancreatology. 2020 Oct;20(7):1354-1367. doi: 10.1016/j.pan.2020.09.001. Epub 2020 Sep 7.
Since the description of the SPINK1 gene encoding the serine protease inhibitor Kazal type 1 and the CTRC gene encoding the Chymotrypsin C as being involved in chronic pancreatitis, more than 56 SPINK1 and 87 CTRC variants have been reported. Assessing the clinical relevance of SPINK1 and CTRC variants is often complicated in the absence of functional evidence and interpretation of rare variants is not very easy in clinical practice. The aim of this study was to review the different variants identified in these two genes and to classify them according to their degree of damaging effect. This classification was based on the results of in vitro experiments, in silico analysis using different prediction tools, and on population data, in comparing the allelic frequency of each variant in patients with pancreatitis and in unaffected control individuals. This review should help geneticists and clinicians in charge of patient's care and genetic counseling to interpret the results of genetic studies.
自从描述了编码丝氨酸蛋白酶抑制剂 Kazal 型 1（SPINK1 基因）和糜蛋白酶 C（CTRC 基因）的基因参与慢性胰腺炎以来，已经报道了超过 56 种 SPINK1 和 87 种 CTRC 变体。在缺乏功能证据的情况下，评估 SPINK1 和 CTRC 变体的临床相关性往往很复杂，并且在临床实践中对罕见变体的解释也不是很容易。本研究的目的是回顾这两个基因中鉴定出的不同变体，并根据其损伤效应的程度对它们进行分类。这种分类是基于体外实验的结果、使用不同预测工具的计算机分析以及人群数据，比较每个变体在胰腺炎患者和未受影响的对照个体中的等位基因频率。本综述应该有助于负责患者护理和遗传咨询的遗传学家和临床医生解释遗传研究的结果。
