PDF(Pubmed)
Abstract：
UNASSIGNED: Emerging data reveal higher-than-expected prevalence of cystic fibrosis (CF) among non-European populations worldwide including in the Indian subcontinent. Systematic analyses of the CFTR mutation profile, and genotype-phenotype correlations among people with CF from south, east, or northeast India have not been reported before. We wanted to identify CFTR mutations in people with CF, and highlight novel variants, selective phenotypic correlations, and regional variances within India.
UNASSIGNED: A retrospective study was conducted at Christian Medical College, Vellore, India (single tertiary referral hospital) from September 2010 to August 2022, involving 120 people with CF from (i) four south Indian states (Tamil Nadu, Andhra Pradesh, Kerala, Karnataka), (ii) in and nearby regions of West Bengal, India and (iii) Bangladesh. Comprehensive CFTR mutation analyses were done by Next-Generation Sequencing, and variants were categorized per American College of Medical Genetics guidelines and compared with validated Locus-specific databases. Demographic characteristics, mutation profile, novel mutations, selective phenotype correlations, and regional variances were assessed.
UNASSIGNED: In 120 people with CF, 55 CFTR variants were identified, including six novel variants. F508del was the predominant mutation, yet with a lower allele frequency than reported among European populations (27% versus 70%). Phenotypic correlations suggested high mutational pathogenicity causing severe multi-organ morbidity, and death in 27%. Milder variants associated with pancreatic sufficiency were also evident in 23% of people with CF. Statistically significant regional variances were noted in genotype frequency, and clinical phenotype among people with CF from the two regions. Hotspot exons and introns that could potentially help create targeted mutation panels were identified.
UNASSIGNED: The identification of 55 different CFTR variants among 120 people with CF describes the diversity of mutations noted in India, while also revealing the challenges that providers may encounter in timely diagnosis and treatment of CF. However, these single-centre data have specific limitations and cannot be generalised to all people with CF from India or to those of non-European origin. Our data on regional CFTR mutations contribute to the emerging national registry on CF epidemiology in India, help formulate diagnostic and newborn screening algorithms, help optimise clinical care, and highlight urgency to improve access to life-changing modulator therapy.
UNASSIGNED: Cystic Fibrosis Foundation, USA (towards the CF-India Demonstration Project) and Christian Medical College, Vellore, India.
UNASSIGNED: A retrospective study was conducted at Christian Medical College, Vellore, India (single tertiary referral hospital) from September 2010 to August 2022, involving 120 people with CF from (i) four south Indian states (Tamil Nadu, Andhra Pradesh, Kerala, Karnataka), (ii) in and nearby regions of West Bengal, India and (iii) Bangladesh. Comprehensive CFTR mutation analyses were done by Next-Generation Sequencing, and variants were categorized per American College of Medical Genetics guidelines and compared with validated Locus-specific databases. Demographic characteristics, mutation profile, novel mutations, selective phenotype correlations, and regional variances were assessed.
UNASSIGNED: In 120 people with CF, 55 CFTR variants were identified, including six novel variants. F508del was the predominant mutation, yet with a lower allele frequency than reported among European populations (27% versus 70%). Phenotypic correlations suggested high mutational pathogenicity causing severe multi-organ morbidity, and death in 27%. Milder variants associated with pancreatic sufficiency were also evident in 23% of people with CF. Statistically significant regional variances were noted in genotype frequency, and clinical phenotype among people with CF from the two regions. Hotspot exons and introns that could potentially help create targeted mutation panels were identified.
UNASSIGNED: The identification of 55 different CFTR variants among 120 people with CF describes the diversity of mutations noted in India, while also revealing the challenges that providers may encounter in timely diagnosis and treatment of CF. However, these single-centre data have specific limitations and cannot be generalised to all people with CF from India or to those of non-European origin. Our data on regional CFTR mutations contribute to the emerging national registry on CF epidemiology in India, help formulate diagnostic and newborn screening algorithms, help optimise clinical care, and highlight urgency to improve access to life-changing modulator therapy.
UNASSIGNED: Cystic Fibrosis Foundation, USA (towards the CF-India Demonstration Project) and Christian Medical College, Vellore, India.
摘要：
■新数据显示，在包括印度次大陆在内的全球非欧洲人群中，囊性纤维化（CF）的患病率高于预期。CFTR突变谱的系统分析，来自南方的CF人群之间的基因型-表型相关性，东,或者印度东北部以前没有报道过。我们想确定CF患者的CFTR突变，突出新颖的变体，选择性表型相关性，以及印度境内的区域差异。
■在基督教医学院进行了一项回顾性研究，Vellore,2010年9月至2022年8月，印度（单一三级转诊医院），涉及来自（i）印度南部四个州（泰米尔纳德邦，安得拉邦,喀拉拉邦,卡纳塔克邦)，（ii）在西孟加拉邦及其附近地区，印度和(三)孟加拉国。全面的CFTR突变分析是通过下一代测序完成的，和变异体按照美国医学遗传学学会指南进行分类,并与经过验证的位点特异性数据库进行比较.人口特征，突变谱,新的突变,选择性表型相关性，并评估了区域差异。
■在120名CF患者中，鉴定了55种CFTR变体，包括六个新颖的变体。F508del是主要突变，然而，等位基因频率低于欧洲人群(27%对70%)。表型相关性表明高突变致病性导致严重的多器官发病率，27%的人死亡。在23％的CF患者中，与胰腺充足相关的轻度变异也很明显。基因型频率具有统计学意义的区域差异，和来自这两个地区的CF患者的临床表型。鉴定了可能有助于产生靶向突变组的热点外显子和内含子。
■在120名CF患者中鉴定出55种不同的CFTR变体，描述了印度发现的突变的多样性，同时也揭示了提供者在及时诊断和治疗CF时可能遇到的挑战。然而,这些单中心数据具有特定的局限性，不能推广到所有来自印度或非欧洲血统的CF患者。我们关于区域CFTR突变的数据有助于印度新兴的CF流行病学国家注册，帮助制定诊断和新生儿筛查算法，帮助优化临床护理，并强调迫切需要改善获得改变生活的调制疗法。
■囊性纤维化基础，美国（走向CF-印度示范项目）和基督教医学院，Vellore,印度。
■在基督教医学院进行了一项回顾性研究，Vellore,2010年9月至2022年8月，印度（单一三级转诊医院），涉及来自（i）印度南部四个州（泰米尔纳德邦，安得拉邦,喀拉拉邦,卡纳塔克邦)，（ii）在西孟加拉邦及其附近地区，印度和(三)孟加拉国。全面的CFTR突变分析是通过下一代测序完成的，和变异体按照美国医学遗传学学会指南进行分类,并与经过验证的位点特异性数据库进行比较.人口特征，突变谱,新的突变,选择性表型相关性，并评估了区域差异。
■在120名CF患者中，鉴定了55种CFTR变体，包括六个新颖的变体。F508del是主要突变，然而，等位基因频率低于欧洲人群(27%对70%)。表型相关性表明高突变致病性导致严重的多器官发病率，27%的人死亡。在23％的CF患者中，与胰腺充足相关的轻度变异也很明显。基因型频率具有统计学意义的区域差异，和来自这两个地区的CF患者的临床表型。鉴定了可能有助于产生靶向突变组的热点外显子和内含子。
■在120名CF患者中鉴定出55种不同的CFTR变体，描述了印度发现的突变的多样性，同时也揭示了提供者在及时诊断和治疗CF时可能遇到的挑战。然而,这些单中心数据具有特定的局限性，不能推广到所有来自印度或非欧洲血统的CF患者。我们关于区域CFTR突变的数据有助于印度新兴的CF流行病学国家注册，帮助制定诊断和新生儿筛查算法，帮助优化临床护理，并强调迫切需要改善获得改变生活的调制疗法。
■囊性纤维化基础，美国（走向CF-印度示范项目）和基督教医学院，Vellore,印度。
