PDF(Pubmed)
Abstract：
UNASSIGNED: Patients with autosomal dominant tubulointerstitial kidney disease (ADTKD) usually present with nonspecific progressive chronic kidney disease (CKD) with mild to negative proteinuria and a family history. ADTKD-MUC1 leads to the formation of a frameshift protein that accumulates in the cytoplasm, leading to tubulointerstitial damage. ADTKD-MUC1 prevalence remains unclear because MUC1 variants are not routinely detected by standard next-generation sequencing (NGS) techniques.
UNASSIGNED: We developed a bioinformatic counting script that can detect specific genetic sequences and count the number of occurrences. We used DNA samples from 27 patients for validation, 11 of them were patients from the Lille University Hospital in France and 16 were from the Wake Forest Hospital, NC. All patients from Lille were tested with an NGS gene panel with our script and all patients from Wake Forest Hospital were tested with the snapshot reference technique. Between January 2018 and February 2023, we collected data on all patients diagnosed with MUC1 variants with this script.
UNASSIGNED: A total of 27 samples were tested anonymously by the BROAD Institute reference technique for confirmation and we were able to get a 100% concordance for MUC1 diagnosis. Clinico-biologic characteristics in our cohort were similar to those previously described in ADTKD-MUC1.
UNASSIGNED: We describe a new simple and cost-effective method for molecular testing of ADTKD-MUC1. Genetic analyses in our cohort suggest that MUC1 might be the first cause of ADTKD. Increasing the availability of MUC1 diagnosis tools will contribute to a better understanding of the disease and to the development of specific treatments.
UNASSIGNED: We developed a bioinformatic counting script that can detect specific genetic sequences and count the number of occurrences. We used DNA samples from 27 patients for validation, 11 of them were patients from the Lille University Hospital in France and 16 were from the Wake Forest Hospital, NC. All patients from Lille were tested with an NGS gene panel with our script and all patients from Wake Forest Hospital were tested with the snapshot reference technique. Between January 2018 and February 2023, we collected data on all patients diagnosed with MUC1 variants with this script.
UNASSIGNED: A total of 27 samples were tested anonymously by the BROAD Institute reference technique for confirmation and we were able to get a 100% concordance for MUC1 diagnosis. Clinico-biologic characteristics in our cohort were similar to those previously described in ADTKD-MUC1.
UNASSIGNED: We describe a new simple and cost-effective method for molecular testing of ADTKD-MUC1. Genetic analyses in our cohort suggest that MUC1 might be the first cause of ADTKD. Increasing the availability of MUC1 diagnosis tools will contribute to a better understanding of the disease and to the development of specific treatments.
摘要：
■常染色体显性肾小管间质性肾病（ADTKD）患者通常表现为非特异性进行性慢性肾病（CKD），有轻度至阴性蛋白尿和家族史。ADTKD-MUC1导致在细胞质中积累的移码蛋白的形成，导致肾小管间质损伤。ADTKD-MUC1的流行率仍不清楚，因为MUC1变异体不能通过标准的下一代测序（NGS）技术常规检测。
■我们开发了一种生物信息学计数脚本，该脚本可以检测特定的遗传序列并对出现的次数进行计数。我们使用了27名患者的DNA样本进行验证，其中11人来自法国里尔大学医院，16人来自威克森林医院，NC。所有来自里尔的患者都用我们的脚本进行了NGS基因面板测试，所有来自威克森林医院的患者都用快照参考技术进行了测试。在2018年1月至2023年2月之间，我们收集了使用此脚本诊断为MUC1变体的所有患者的数据。
■通过BROADInstitute参考技术对总共27个样本进行了匿名测试，以进行确认，我们能够获得MUC1诊断的100％一致性。我们队列中的临床生物学特征与先前在ADTKD-MUC1中描述的相似。
■我们描述了一种用于ADTKD-MUC1分子测试的新的简单且经济有效的方法。我们队列中的遗传分析表明MUC1可能是ADTKD的第一个原因。增加MUC1诊断工具的可用性将有助于更好地了解疾病和开发特定的治疗方法。
■我们开发了一种生物信息学计数脚本，该脚本可以检测特定的遗传序列并对出现的次数进行计数。我们使用了27名患者的DNA样本进行验证，其中11人来自法国里尔大学医院，16人来自威克森林医院，NC。所有来自里尔的患者都用我们的脚本进行了NGS基因面板测试，所有来自威克森林医院的患者都用快照参考技术进行了测试。在2018年1月至2023年2月之间，我们收集了使用此脚本诊断为MUC1变体的所有患者的数据。
■通过BROADInstitute参考技术对总共27个样本进行了匿名测试，以进行确认，我们能够获得MUC1诊断的100％一致性。我们队列中的临床生物学特征与先前在ADTKD-MUC1中描述的相似。
■我们描述了一种用于ADTKD-MUC1分子测试的新的简单且经济有效的方法。我们队列中的遗传分析表明MUC1可能是ADTKD的第一个原因。增加MUC1诊断工具的可用性将有助于更好地了解疾病和开发特定的治疗方法。
