Iwańczak Franciszek, Smigiel Robert, Stawarski Andrzej, Pawłowicz Janina, Stembalska Agnieszka, Mowszet Krystyna, Sasiadek Maria
Klinika Pediatrii, Gastroenterologii i Zywienia AM we Wrocławiu.
Pol Merkur Lekarski. 2005 Feb;18(104):205-9.
Cystic fibrosis is the most common autosomal recessive genetic defect of one gene CFTR, where a variety of mutations were revealed. Cystic fibrosis is a variable disease and to date the genotype-phenotype correlation is difficult to clarify. The aim of the study was to analyse retrospectively the genotype and phenotype of children with cystic fibrosis and to search the correlation between type of mutation in CFTR and clinical manifestation of the gastrointestinal tract.
The study group comprised 52 patients. Molecular DNA analyses were performed in 43 cases. Statistical analysis was done by using Fisher test.
In 34 (79%) cases two mutations in the CFTR gene were identified. In this group 21 cases were identified as a homozygous for AF508 mutation, in single case other mutations were found. A mutation of one CFTR allel was revealed in 11 patients, cystic fibrosis was not confirmed by genetic test in 9 children. Mean age of diagnosis was 34 months. In 38 children (73%) pancreatic insufficiency in the course of disease was found. Exocrine insufficiency of pancreas was showed significant frequently in homozygous group. Liver dysfunction in 20 children (38.5%) was revealed. In this group 12 patients was identified as a homozygous for deltaF508 mutation. On the base of oral glucose tolerance test the diabetes mellitus and glucose intolerance was diagnosed in 4 cases with homozygous genotype. Seven patients died in the endstage of the illness, in two of them homozygous mutation deltaF508 was found, in next 5 patients genetic analysis was not performed.
The frequency and severity of clinical manifestation of the gastrointestinal tract correlates with deltaF508 mutation. Early genetic test and demonstration of molecular defect in CFTR gene confirms the clinical diagnosis of cystic fibrosis and improves a quality of life and prolongs survival time of cystic fibrosis patients.
囊性纤维化是一种最常见的由CFTR单基因引起的常染色体隐性遗传缺陷疾病，已发现多种突变。囊性纤维化是一种具有多种表现的疾病，迄今为止，基因型与表型之间的相关性难以阐明。本研究的目的是回顾性分析囊性纤维化患儿的基因型和表型，并探寻CFTR基因突变类型与胃肠道临床表现之间的相关性。
研究组包括52例患者。对其中43例进行了分子DNA分析。采用Fisher检验进行统计分析。
在34例（79%）病例中鉴定出CFTR基因的两个突变。在该组中，21例被鉴定为AF508突变纯合子，仅1例发现其他突变。11例患者发现一个CFTR等位基因发生突变，9名儿童的基因检测未确诊为囊性纤维化。平均诊断年龄为34个月。38例儿童（73%）在病程中发现胰腺功能不全。胰腺外分泌功能不全在纯合子组中显著常见。20例儿童（38.5%）出现肝功能障碍。该组中有12例患者被鉴定为deltaF508突变纯合子。根据口服葡萄糖耐量试验，4例纯合子基因型患者被诊断为糖尿病和葡萄糖不耐受。7例患者在疾病终末期死亡，其中2例发现纯合子突变deltaF508，另外5例未进行基因分析。
胃肠道临床表现的频率和严重程度与deltaF508突变相关。早期基因检测及CFTR基因分子缺陷的证实有助于囊性纤维化的临床诊断，提高患者生活质量并延长其生存时间。
