Evaluating DNA methylation episignatures as a first-tier diagnostic test in individuals with suspected genetic disorders.

IF 4.6 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Tinatin Tkemladze, Christopher Campbell, Kakha Bregvadze, Eka Kvaratskhelia, Elene Abzianidze, Leigh Demain, Sarah Jenkinson, Sarah Hilton, Michael Levy, Jennifer Kerkhof, David Gokhale, Bekim Sadikovic, Siddharth Banka
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引用次数: 0

Abstract

DNA methylation (DNAm) episignature analysis is an emerging tool for diagnosing individuals with neurodevelopmental disorders, congenital anomalies, and growth disorders. We evaluated its clinical utility as a first-tier test in 62 individuals without prior molecular testing. DNAm arrays identified a diagnosis in 30.6% (19/62) of cases. The positivity rate was highest for Fragile X syndrome (100%, 5/5), followed by syndromic disorders (44%, 8/18) and imprinting disorders (25%, 6/24), including Silver-Russell, Beckwith-Wiedemann, and Prader-Willi syndromes. No diagnoses were made in 15 individuals with non-syndromic neurodevelopmental disorders. Alternative diagnoses were identified in 4.8% (3/62) of cases. These findings suggest that DNAm arrays can serve as an effective first-tier diagnostic tool, particularly for syndromic and imprinting disorders, with potential to improve diagnostic efficiency and reduce reliance on sequential genetic testing. While these findings support the use of DNAm arrays as an effective first-tier tool in selected populations, larger, unselected cohort studies are needed to validate its generalizability.

评估DNA甲基化表观特征作为疑似遗传疾病个体的一级诊断测试。
DNA甲基化(DNAm)特征分析是一种新兴的诊断神经发育障碍、先天性异常和生长障碍的工具。我们评估了它作为一级测试在62个人没有事先分子检测的临床效用。在30.6%(19/62)的病例中,脱氧核糖核酸阵列确诊。脆性X综合征的阳性率最高(100%,5/5),其次是综合征性疾病(44%,8/18)和印迹性疾病(25%,6/24),包括银罗素综合征、贝克威斯曼综合征和普雷德-威利综合征。15名非综合征性神经发育障碍患者未被诊断。4.8%(3/62)的病例有其他诊断。这些发现表明,dna阵列可以作为一种有效的一线诊断工具,特别是对于综合征和印记疾病,具有提高诊断效率和减少对序列基因检测依赖的潜力。虽然这些发现支持DNAm阵列在选定人群中作为有效的一线工具,但需要更大规模的非选定队列研究来验证其普遍性。
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来源期刊
European Journal of Human Genetics
European Journal of Human Genetics 生物-生化与分子生物学
CiteScore
9.90
自引率
5.80%
发文量
216
审稿时长
2 months
期刊介绍: The European Journal of Human Genetics is the official journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports and reviews in the rapidly expanding field of human genetics and genomics. It covers molecular, clinical and cytogenetics, interfacing between advanced biomedical research and the clinician, and bridging the great diversity of facilities, resources and viewpoints in the genetics community. Key areas include: -Monogenic and multifactorial disorders -Development and malformation -Hereditary cancer -Medical Genomics -Gene mapping and functional studies -Genotype-phenotype correlations -Genetic variation and genome diversity -Statistical and computational genetics -Bioinformatics -Advances in diagnostics -Therapy and prevention -Animal models -Genetic services -Community genetics
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