Sobczyńska-Tomaszewska Agnieszka, Bak Daniel, Oralewska Beata, Oracz Grzegorz, Norek Aleksandra, Czerska Kamila, Mazurczak Tadeusz, Teisseyre Mikołaj, Socha Jerzy, Zagulski Marek, Bal Jerzy
Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
J Pediatr Gastroenterol Nutr. 2006 Sep;43(3):299-306. doi: 10.1097/01.mpg.0000232570.48773.df.
Defects of PRSS1, SPINK1, CFTR and AAT are considered causative or predisposing to pancreatitis. The aim of this study was to evaluate the impact of these defects into molecular pathology of chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP).
Ninety-two children with CP or ARP, 55 family members and 50 controls were investigated. The subjects were screened for PRSS1 mutations: R122H, R122C, A16V, N29I; SPINK1 N34S variant; panel of 14 CFTR defects: INNOLiPA CFTR12, CFTRdele2,3 and IVS8-T variant or panel of 3 CFTR defects-F508del, CFTRdele2,3 and IVS8-T; AAT mutations: E264V, E342K.
We identified 1 mutated allele in at least 1 of 4 genes in 31 of 92 patients and 12 of 50 controls (P = 0.157). Mutations in SPINK1 and PRSS1 were most frequent. PRSS1 mutations were identified mainly in CP patients (9.6% of CP vs 2.5% of ARP alleles, P = 0.094), whereas N34S SPINK1 mutation was present with comparable frequency in CP and ARP patients (7.7% vs 10.0%, P = 0.768). The frequency of mutations in CFTR alleles was similar to controls (4.9% vs 5%, P = 0.587). Overall frequency of AAT mutations was lower than in the controls. Family studies showed that defects in the examined genes did not always segregate with disease.
PRSS1 defects seem to be causative for pancreatitis, whereas defects in SPINK1 are suggested to be associated with the disease. No association between CFTR mutations and pancreatitis was observed. The importance of AAT variants remains speculative.
PRSS1、SPINK1、CFTR和AAT的缺陷被认为是胰腺炎的病因或易感因素。本研究的目的是评估这些缺陷对慢性胰腺炎（CP）和急性复发性胰腺炎（ARP）分子病理学的影响。
对92例CP或ARP患儿、55名家庭成员和50名对照进行了调查。对受试者进行PRSS1突变筛查：R122H、R122C、A16V、N29I；SPINK1 N34S变异；14种CFTR缺陷组合：INNOLiPA CFTR12、CFTRdele2,3和IVS8-T变异，或3种CFTR缺陷组合-F508del、CFTRdele2,3和IVS8-T；AAT突变：E264V、E342K。
在92例患者中的31例和50例对照中的12例中，我们在4个基因中的至少1个基因中鉴定出1个突变等位基因（P = 0.157）。SPINK1和PRSS1中的突变最为常见。PRSS1突变主要在CP患者中鉴定到（CP等位基因的9.6% 对ARP等位基因的2.5%，P = 0.094），而N34S SPINK1突变在CP和ARP患者中的出现频率相当（7.7% 对10.0%，P = 0.768）。CFTR等位基因突变频率与对照相似（4.9% 对5%，P = 0.587）。AAT突变的总体频率低于对照。家系研究表明，所检测基因的缺陷并不总是与疾病共分离。
PRSS1缺陷似乎是胰腺炎的病因，而SPINK1缺陷提示与该疾病相关。未观察到CFTR突变与胰腺炎之间的关联。AAT变异的重要性仍具有推测性。
