背景:在新生儿筛查不足的高度多种族人群中,了解囊性纤维化(CF)的各种表型表现可以帮助早期诊断。这项研究旨在描述巴西东北地区一个州CF诊断时的表型和基因型。
方法:回顾性横断面研究。从CF患者的病历中提取临床数据。临床,实验室,我们描述了2007年至2021年间进入三级转诊中心的患者的基因型特征.
结果:58名患者被纳入研究,其中53.5%是通过临床怀疑确诊的。诊断时的中位年龄为4.7个月(IQR:1.5-14.8个月)。5例患者在新生儿筛查中出现假阴性结果。生长迟缓是最常见的临床表现。支气管扩张和肺炎病史在10岁以上的人群中占主导地位,虽然薄,体重不足,2岁以下儿童的电解质失衡更为常见。CFTR基因测序鉴定出27种基因型,在所有患者中至少有一个I-III类变异,和九种罕见的变种,以前没有描述过,或具有不确定的意义(619delA,T12991,K162Q,3195del6,1678del>T,124del123bp,3121-3113A>T)。最常见的等位基因是p.Phe508del,p.Gly542*,p.Arg334Trp,和p.Ser549Arg.
结论:营养不良和电解质失衡是2岁以下儿童最常见的表型,并与包括2种I-III类变异的基因型相关。鉴定了罕见和以前未描述的变体。p.Gly542*,p.Arg334Trp,p.Ser549Arg等位基因是该人群中最常见的变异。
BACKGROUND: In highly multiracial populations with inadequate newborn screening, knowledge of the various phenotypic presentations of Cystic Fibrosis (CF) can help reach an early diagnosis. This study aims to describe phenotypes and genotypes at the time of CF diagnosis in a state in the Northeast Region of Brazil.
METHODS: Retrospective cross-sectional study. Clinical data were extracted from the medical records of CF patients. Clinical, laboratory, and genotypic characteristics were described for patients admitted to a tertiary referral center between 2007 and 2021.
RESULTS: Fifty-eight (58) patients were included in the study, 53.5% of whom were diagnosed through clinical suspicion. The median age at diagnosis was 4.7 months (IQR: 1.5-14.8 months). Five patients had false-negative results in the newborn screening. Faltering growth was the most frequent clinical manifestation. Bronchiectasis and a history of pneumonia predominated in those older than ten, while thinness, underweight, and electrolyte imbalances were more frequent in children under two. Sequencing of the CFTR gene identified 27 genotypes, with at least one class I-III variant in all patients, and nine variants that are rare, previously undescribed, or have uncertain significance (619delA, T12991, K162Q, 3195del6, 1678del > T, 124del123bp, 3121-3113 A > T). The most frequent alleles were p.Phe508del, p.Gly542*, p.Arg334Trp, and p.Ser549Arg.
CONCLUSIONS: Malnutrition and electrolyte imbalances were the most frequent phenotypes for children < 2 years and were associated with genotypes including 2 class I-III variants. Rare and previously undescribed variants were identified. The p.Gly542*, p.Arg334Trp, and p.Ser549Arg alleles were among the most frequent variants in this population.