Heterogeneity of phenotypic manifestations of cystic fibrosis in children and predictors of the disease severity

IF 0.1 Q4 MEDICINE, GENERAL & INTERNAL
BС С. І К. В. Скрябіна A, Ільченко, F. E
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Abstract

The aim of the study was to investigate the heterogeneity of phenotypic manifestations of cystic fibrosis (CF) in children depending on the CFTR gene mutation and to determine predictors of the disease severity for the personalization of treatment and prevention of complications. Materials and methods. Fifty-nine children with CF, aged 1 to 18 years (mean age was 12.0 (8.5; 15.0) years), were examined. All patients underwent general clinical, genetic, laboratory and microbiological examination. Instrumental methods of examination included spirometry, chest X-ray and computed tomography, ultrasound densitometry. According to the functional effects of CFTR mutations, the patients were divided into two groups. The group with “severe” genotypes (n = 40) included patients with two class I and/or II mutations, and the group with “mild” genotypes (n = 10) included patients with at least one class IV or V mutation. Mutations were not identified in 9 patients. Results. Analysis of the spectrum of genetic variants in the CFTR gene showed that 10 patients (20.0 %) were identified with the “mild” genotype, and 40 patients (80.0 %) with the “severe” genotype. The most common mutation was F508del predominantly in the compound heterozygous state (42.4 %). It was found that patients with the “mild” genotype were characterized by a more favorable course of the disease than patients with the “severe” genotype. No statistically significant phenotypic features of the CF course in children depending on the F508del mutation status (F508del/F508del or F508del/nonF508del) were found, except for earlier formation of pulmonary hypertension in patients with the homozygous condition (47.1% vs 16.0 %, P < 0.05). Conclusions. Examination of the relationship between CFTR genotype and phenotype has revealed associations between CFTR mutations and lesion severity of both the digestive and bronchopulmonary systems. Identification of disease severity predictors can provide a more accurate prediction of the disease course, that will determine the patient management and prevent the development of complications.
儿童囊性纤维化表型表现的异质性和疾病严重程度的预测因子
该研究的目的是调查儿童囊性纤维化(CF)表型表现的异质性,这取决于CFTR基因突变,并确定疾病严重程度的预测因素,以便个性化治疗和预防并发症。材料和方法。59例CF患儿,年龄1 ~ 18岁(平均年龄12.0岁;15.0岁),接受了检查。所有患者均接受一般临床、遗传学、实验室和微生物学检查。仪器检查方法包括肺活量测定、胸部x线和计算机断层扫描、超声密度测定。根据CFTR突变对功能的影响,将患者分为两组。“严重”基因型组(n = 40)包括两个I类和/或II类突变的患者,“轻度”基因型组(n = 10)包括至少一个IV类或V类突变的患者。9例患者未发现突变。CFTR基因变异谱分析显示,10例(20.0%)患者为“轻度”基因型,40例(80.0%)患者为“重度”基因型。最常见的突变是F508del,主要发生在复合杂合状态(42.4%)。结果发现,“轻度”基因型患者的病程比“重度”基因型患者的病程更有利。F508del突变状态(F508del/F508del或F508del/非F508del)在儿童CF病程中未发现统计学上显著的表型特征,但纯合子状态患者更早形成肺动脉高压(47.1% vs 16.0%, P < 0.05)。对CFTR基因型和表型之间关系的研究揭示了CFTR突变与消化系统和支气管肺系统病变严重程度之间的关联。识别疾病严重程度预测因子可以更准确地预测病程,从而确定患者的治疗方法并预防并发症的发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Zaporozhye Medical Journal
Zaporozhye Medical Journal MEDICINE, GENERAL & INTERNAL-
自引率
0.00%
发文量
72
审稿时长
8 weeks
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