通过基因组测序在疑似罕见疾病的个体中鉴定出多种分子诊断。

IF 3.3 Q2 GENETICS & HEREDITY
Alka Malhotra, Erin Thorpe, Alison J Coffey, Revathi Rajkumar, Josephine Adjeman, Naomi Dianne Naa Adjeley Adjetey, Sharron Aglobitse, Felix Allotey, Todor Arsov, Joyce Ashong, Ebenezer Vincent Badoe, Donald Basel, Yvonne Brew, Chester Brown, Kerri Bosfield, Kari Casas, Mario Cornejo-Olivas, Laura Davis-Keppen, Abbey Freed, Kate Gibson, Parul Jayakar, Marilyn C Jones, Martina Kawome, Aimé Lumaka, Ursula Maier, Prince Makay, Gioconda Manassero, Marilyn Marbell-Wilson, Charles Marcuccilli, Diane Masser-Frye, Julie McCarrier, Hannah-Sharon Mills, Jeny Balazar Montoya, Gerrye Mubungu, Mamy Ngole, Jorge Perez, Eniko Pivnick, Milagros M Duenas-Roque, Hildegard Pena Salguero, Arturo Serize, Marwan Shinawi, Fabio Sirchia, Claudia Soler-Alfonso, Alan Taylor, Lauren Thompson, Gail Vance, Adeline Vanderver, Keith Vaux, Danita Velasco, Samuel Wiafe, Ryan J Taft, Denise L Perry, Akanchha Kesari
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引用次数: 0

摘要

基因组测序是一种强大而全面的检测方法,可以检测到不同类型的多种变异。对整个基因组的变异进行分析,可以在单个个体中识别多分子诊断(MMDs)。在这项回顾性研究中,我们描述了烟雾病与先证者的检测指征(IFT)、继发发现或偶然发现相关的个体。如果至少有一项发现与原发性IFT相关,并且所有变异都被归类为可能致病或致病,则被认为是烟雾病。作为iHope项目的一部分,在2017年9月至2023年12月期间,Illumina实验室服务对所有个体进行了临床基因组测序。iHope队列包括1846名受影响的个体,其中872名(47.2%)发现至少有一种与原发性IFT相关的可能致病性或致病性变异。其中,81人(9.3%)有多种临床显著的分子发现,包括76人报告的与两种不同疾病相关的变异,5人有两种以上的分子发现。32人(3.7%)至少有两种与原发性IFT相关的分子诊断,而49人(5.6%)报告的第二种情况的变异构成了次要或偶然发现。我们的研究强调,在通过基因组测序鉴定出可能具有致病性或致病性的个体中,有9%的人患有MMDs,这可能是不同的检测方法所遗漏的。值得注意的是,在81名烟雾病患者中,大约60%的人有潜在的可操作的继发或偶然发现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multiple molecular diagnoses identified through genome sequencing in individuals with suspected rare disease.

Genome sequencing is a powerful and comprehensive test that detects multiple variants of different types. The interrogation of variants across the genome enables the identification of multiple molecular diagnoses (MMDs) in a single individual. In this retrospective study, we describe individuals in whom MMDs were associated with the proband's indication for testing (IFT), secondary findings, or incidental findings. An MMD is considered where at least one of the findings is associated with the primary IFT and all variants are classified as either likely pathogenic or pathogenic. Clinical genome sequencing was performed for all individuals as part of the iHope program at the Illumina Laboratory Services between September 2017 and December 2023. The iHope cohort included 1,846 affected individuals, with 872 (47.2%) found to have at least one likely pathogenic or pathogenic variant associated with the primary IFT. Of these, 81 (9.3%) individuals had multiple clinically significant molecular findings, including 76 individuals with reported variants associated with 2 different conditions, and 5 individuals with more than 2 molecular findings. A total of 32 individuals (3.7%) had at least 2 molecular diagnoses related to the primary IFT, while in 49 (5.6%) individuals, the variant(s) reported for the second condition constituted a secondary or incidental finding. Our study highlights that among individuals with a likely pathogenic or pathogenic finding identified through genome sequencing, 9% have MMDs, which may have been missed with different testing methods. Of note, approximately 60% of the 81 individuals with an MMD had a potentially actionable secondary or incidental finding.

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来源期刊
HGG Advances
HGG Advances Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
4.30
自引率
4.50%
发文量
69
审稿时长
14 weeks
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