Small Supernumerary Marker Chromosomes in Humans: From Classical Cytogenetics to High-Resolution Cytogenomics
- 1Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia
- 2Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
Abstract
Small supernumerary marker chromosomes (sSMCs) are additional chromosomal elements smaller than or equal to chromosome 20, with a prevalence of ~0.044% in the population. Their clinical impact ranges from asymptomatic carriage to severe congenital, neurodevelopmental, and other disorders. Accurate diagnosis and interpretation remain challenging due to their small physical size, frequent tissue-specific mosaicism, and variable expression of similar gene content across different genetic backgrounds, which is well known for numerous clinically significant gene variants. This review synthesizes current knowledge on sSMC biology, diagnostics, and clinical management, highlighting the paradigm shift from classical cytogenetics to high-resolution genomic and cytogenomic approaches, including long-read genome sequencing combined with telomere-to-telomere chromosome assemblies. We present an updated sSMC classification based on sSMC DNA content and structural organization, discuss molecular mechanisms of sSMC biogenesis, and critically evaluate the diagnostic utility of microarray comparative genomic hybridization, whole-genome sequencing, and chromosome microdissection-based approaches. We also discuss breakpoint positions in sSMC formation, sSMC localization in nuclear spatial compartments, and tissue distribution patterns as factors with possible influence on the sSMC manifestation. Some of these properties might be used as criteria for assessing the pathogenic potential of sSMCs, while others require further investigation. Furthermore, we refine pathogenicity assessment frameworks by incorporating sSMC content and morphology. By integrating cutting-edge molecular cytogenetics with standardized interpretive guidelines, this narrative review provides a useful framework for precise sSMC characterization, which is essential for genetic counseling and targeted clinical management.
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BibTeX
@article{rubtsov2026small,
title = {{Small Supernumerary Marker Chromosomes in Humans: From Classical Cytogenetics to High-Resolution Cytogenomics}},
author = {Nikolay B. Rubtsov and Tatyana V. Karamysheva and Anna A. Kashevarova and Igor N. Lebedev},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219812},
url = {https://www.mdpi.com/1422-0067/27/21/9812},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Small Supernumerary Marker Chromosomes in Humans: From Classical Cytogenetics to High-Resolution Cytogenomics
AU - Nikolay B. Rubtsov
AU - Tatyana V. Karamysheva
AU - Anna A. Kashevarova
AU - Igor N. Lebedev
PY - 2026
DA - 2026/11/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219812
UR - https://www.mdpi.com/1422-0067/27/21/9812
AB - Small supernumerary marker chromosomes (sSMCs) are additional chromosomal elements smaller than or equal to chromosome 20, with a prevalence of ~0.044% in the population. Their clinical impact ranges from asymptomatic carriage to severe congenital, neurodevelopmental, and other disorders. Accurate diagnosis and interpretation remain challenging due to their small physical size, frequent tissue-specific mosaicism, and variable expression of similar gene content across different genetic backgrounds, which is well known for numerous clinically significant gene variants. This review synthesizes current knowledge on sSMC biology, diagnostics, and clinical management, highlighting the paradigm shift from classical cytogenetics to high-resolution genomic and cytogenomic approaches, including long-read genome sequencing combined with telomere-to-telomere chromosome assemblies. We present an updated sSMC classification based on sSMC DNA content and structural organization, discuss molecular mechanisms of sSMC biogenesis, and critically evaluate the diagnostic utility of microarray comparative genomic hybridization, whole-genome sequencing, and chromosome microdissection-based approaches. We also discuss breakpoint positions in sSMC formation, sSMC localization in nuclear spatial compartments, and tissue distribution patterns as factors with possible influence on the sSMC manifestation. Some of these properties might be used as criteria for assessing the pathogenic potential of sSMCs, while others require further investigation. Furthermore, we refine pathogenicity assessment frameworks by incorporating sSMC content and morphology. By integrating cutting-edge molecular cytogenetics with standardized interpretive guidelines, this narrative review provides a useful framework for precise sSMC characterization, which is essential for genetic counseling and targeted clinical management.
SN - 1422-0067
ER -