Long read human traslocation on NF2 gene
The identification of structural variant (SV) breakpoints plays a crucial role in understanding the mutations, mutagenic mechanisms, and functional consequences that drive various genetic diseases. While next-generation sequencing (NGS) has become a cornerstone in single nucleotide variant (SNP) discovery and characterization, short-read NGS technology faces significant challenges in resolving large genomic rearrangements such as duplications, deletions, inversions, and translocations. Nanopore sequencing offers a promising alternative by enabling the precise breakpoints of chromosomal rearrangements, dramatically enhancing the accuracy of diagnosing genetic diseases associated with chromosomal alterations. Using long-read whole-genome sequencing, we examined the breakpoints of a cytogenetically balanced chromosomal translocation, t(8;22)(q13.3;q11.23), initially detected during prenatal diagnosis and later confirmed as de novo in a patient who developed NF2-associated schwannomatosis in late infancy. Nanopore sequencing revealed that the translocation disrupted the NF2 gene. This case highlights the power of nanopore long-read sequencing in detecting the exact consequences of de novo, apparently balanced translocations and in uncovering the genetic underpinnings of abnormal phenotypes. Given its ability to resolve complex SVs with high precision, nanopore sequencing might be considered a valuable complement to conventional genetic diagnostic methods, enhancing our understanding of genetic diseases and potentially improving clinical outcomes.