Genomic Testing in Adults With Undiagnosed Rare Conditions: Improvement of Diagnosis Using Clinical Exome Sequencing as a First-Tier Approach.

IF 2.9 3区 医学 Q2 GENETICS & HEREDITY
Roberta Petillo, Ilaria De Maggio, Carmelo Piscopo, Massimiliano Chetta, Marina Tarsitano, Luigi Chiriatti, Elvira Sannino, Serena Torre, Marcella D'Antonio, Paola D'Ambrosio, Marco Rambaldi, Maria Cioce, Valentina De Stefano, Maria Rita Parisi, Antonella Telese, Maria Oro, Maria Rivieccio, Francesca Clementina Radio, Cecilia Mancini, Marcello Niceta, Viviana Cordeddu, Alessandro Bruselles, Corrado Mammì, Adele Dattola, Tiziana Fioretti, Gabriella Esposito, Antonio Novelli, Alessandro Tessitore, Alessandra Tessa, Filippo Maria Santorelli, Achille Iolascon, Matteo Della Monica, Marco Tartaglia, Manuela Priolo
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引用次数: 0

Abstract

Adult patients with undiagnosed genetic disorders suffer most from diagnostic delay and seldom appear in cohort studies investigating the diagnostic yield in medical genetic clinical practice. Here we present the results of the diagnostic activity performed in a referral center on 654 consecutive, unselected adult subjects presenting with molecularly unsolved conditions. More than 50% of the referred individuals were affected by syndromic or isolated intellectual disability. Different molecular approaches, including clinical/whole exome sequencing (CES/WES), chromosomal microarray analysis (CMA), and/or targeted gene or gene panel sequencing were used to analyze patients' DNA. Definitive diagnosis was obtained in over 30% of individuals. The most sensitive methodology was CES/WES, which allowed us to reach a diagnosis in over 50% of the 162 solved cases. Despite the great variety of clinical presentations, our results represent a reliable picture of the "real world" daily routine in an outpatient medical genetics clinic dedicated to diagnostic activity, and contribute to better understand the great value of a definitive molecular diagnosis in adults, either for the affected individuals and their families. This retrospective analysis demonstrates the importance of adopting a genomic-first approach within the diagnostic process for adults affected with unsolved rare conditions.

成人未确诊罕见疾病的基因组检测:使用临床外显子组测序作为一线方法改善诊断。
未确诊遗传疾病的成年患者最常出现诊断延误,在医学遗传学临床实践中很少出现诊断延误的队列研究。在这里,我们提出的诊断活动的结果执行在转诊中心对654连续,未选择的成人受试者呈现分子未解条件。超过50%的转介个体患有综合征或孤立性智力残疾。不同的分子方法,包括临床/全外显子组测序(CES/WES)、染色体微阵列分析(CMA)和/或靶向基因或基因面板测序,用于分析患者的DNA。确诊率超过30%。最敏感的方法是CES/WES,它使我们在162个已解决病例中超过50%的病例中得到诊断。尽管有各种各样的临床表现,我们的结果代表了一个可靠的“真实世界”的日常图景,门诊医学遗传学诊所致力于诊断活动,并有助于更好地理解成人明确的分子诊断的巨大价值,无论是对受影响的个人和他们的家庭。这一回顾性分析证明了在诊断过程中采用基因组优先方法对未解决的罕见疾病的成人的重要性。
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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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