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<p>Chromosomal rearrangements are a major cause of human disorders. They can be numerical or structural abnormalities, and understanding their frequency and nature is vital for accurate diagnosis and genetic counselling. Despite the widespread adoption of sequencing technologies, conventional cytogenetics remains indispensable for detecting balanced and complex rearrangements that often escape array- and sequencing-based approaches. In this study, we combined long-term cytogenetic surveillance with targeted molecular analyses and genome sequencing to characterise the spectrum of chromosomal abnormalities in Southern India and to resolve a novel disease-associated rearrangement. A retrospective analysis of 24,633 cases (1998–2024) was performed using G-banding, C-banding, Ag-NOR staining, FISH, chromosomal microarray, and genome sequencing. In all cases, karyotyping was performed, but FISH/CMA/sequencing was performed in selected cases based on clinical indication. Chromosomal abnormalities were detected in 1,721 (6.9%) cases, and an additional 468 (1.9%) polymorphic variants. Almost 52% were numerical abnormalities, 19% were structural variants, 3% were sex reversal cases, 5% were mosaic variants, and 21% were polymorphic variants. The accurate detection of breakpoint regions in disease-associated rearrangements helps elucidate the molecular mechanisms and thus identify the risks associated with disrupted genes. Importantly, we report a previously undescribed familial double translocation in the mother and an apparent reciprocal translocation in the child, both of which were resolved by FISH and whole-genome sequencing. Sequencing revealed a heterozygous deletion disrupting exons 6–8 of the <i>EFCAB3</i> gene, a neurodevelopmentally relevant gene not detected by microarray, establishing a novel genotype–phenotype correlation. The literature review and the overall yield of chromosomal analysis underscore the significance of conventional cytogenetics. This article aligns with SDG 3 (Good Health and Well-Being) of the UN Agenda for Sustainable Development.</p>

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A 27-year retrospective analysis of 24,633 cases reveals the spectrum of chromosomal abnormalities in Southern India and identifies a novel translocation disrupting EFCAB3

  • 期刊论文

  • 发表日期：

    2026年6月3日

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  • Usha R. Dutta,
  • Rajitha Ponnala,
  • Kritika Ramgopal,
  • Divya Bhanu Nalla,
  • Uzair Ahmed,
  • Vijay Kumar Sunke,
  • Ashwin Dalal

摘要

Chromosomal rearrangements are a major cause of human disorders. They can be numerical or structural abnormalities, and understanding their frequency and nature is vital for accurate diagnosis and genetic counselling. Despite the widespread adoption of sequencing technologies, conventional cytogenetics remains indispensable for detecting balanced and complex rearrangements that often escape array- and sequencing-based approaches. In this study, we combined long-term cytogenetic surveillance with targeted molecular analyses and genome sequencing to characterise the spectrum of chromosomal abnormalities in Southern India and to resolve a novel disease-associated rearrangement. A retrospective analysis of 24,633 cases (1998–2024) was performed using G-banding, C-banding, Ag-NOR staining, FISH, chromosomal microarray, and genome sequencing. In all cases, karyotyping was performed, but FISH/CMA/sequencing was performed in selected cases based on clinical indication. Chromosomal abnormalities were detected in 1,721 (6.9%) cases, and an additional 468 (1.9%) polymorphic variants. Almost 52% were numerical abnormalities, 19% were structural variants, 3% were sex reversal cases, 5% were mosaic variants, and 21% were polymorphic variants. The accurate detection of breakpoint regions in disease-associated rearrangements helps elucidate the molecular mechanisms and thus identify the risks associated with disrupted genes. Importantly, we report a previously undescribed familial double translocation in the mother and an apparent reciprocal translocation in the child, both of which were resolved by FISH and whole-genome sequencing. Sequencing revealed a heterozygous deletion disrupting exons 6–8 of the EFCAB3 gene, a neurodevelopmentally relevant gene not detected by microarray, establishing a novel genotype–phenotype correlation. The literature review and the overall yield of chromosomal analysis underscore the significance of conventional cytogenetics. This article aligns with SDG 3 (Good Health and Well-Being) of the UN Agenda for Sustainable Development.