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.
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