Next-generation sequencing in the diagnosis of monogenic disorders
DOI:
https://doi.org/10.13112/pc.1052Keywords:
HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; NEUROCUTANEOUS SYNDROMES; NOONAN SYNDROME; MARFAN SYNDROME; NEUROFIBROMATOSES;Abstract
Next-generation sequencing (NGS) is essential for diagnosing monogenic disorders, including neurocutaneous syndromes (phakomatoses) and connective tissue syndromes such as Noonan and Marfan syndromes. A retrospective study was conducted from 2022 to 2025 to analyse the application of NGS at the University Hospital Centre Zagreb. A total of 131 patient samples suspected of neurocutaneous syndromes and 94 samples suspected of Noonan or Marfan syndrome were analyzed. The results showed that 25 % of patients clinically suspected of having a neurocutaneous syndrome carried pathogenic variants, with the NF1 gene being the most frequently affected. Among patients with connective tissue syndromes, 23 % had pathogenic mutations, most commonly in the PTPN11 and FBN1 genes. Standard NGS gene panels primarily detect point mutations and small deletions/duplications, while for larger causal alterations, such as NF1 gene deletions, additional MLPA analysis plays a significant diagnostic role in detecting larger deletions that NGS cannot identify. The application of NGS enables more precise diagnosis and differentiation among genetically similar syndromes, improving clinical practice and genetic counseling.
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Copyright (c) 2025 Kristina Crkvenac Gornik, Jadranka Škorput, Ana Juras, Sanda Huljev Frković
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