Molecular cytogenetic identification of small supernumerary marker chromosomes using chromosome microarray analysis

Huili Xue†Email author View ORCID ID profile,
Hailong Huang,
Yan Wang,
Gang An,
Min Zhang,
Liangpu Xu† and
Yuan Lin

†Contributed equally

Molecular Cytogenetics201912:13

https://doi.org/10.1186/s13039-019-0425-5

Received: 22 November 2018
Accepted: 27 February 2019
Published: 11 March 2019

Abstract

Background

This study aimed to evaluate the feasibility of chromosomal microarray analysis (CMA) in detecting the origin and structure of small supernumerary marker chromosomes (sSMCs) in prenatal and postnatal cases and to clarify sSMC-related genotype-phenotype correlations.

Results

Thirty-three cases carrying sSMCs were identified by banding cytogenetics. Of these cases, twenty-nine were first characterized by CMA and only two by FISH. The remaining two cases were excluded for their refusal to accept further examination. The chromosomal origins of twenty-two cases were successfully identified, in which pathogenetic copy number variations (PCNVs) were found in sixteen cases, four cases showed variants of uncertain significance (VOUS), one case showed benign CNVs, and one case showed probable PCNVs. For the nine cases with negative CMA results, only one of them contained centromere heterochromatin likely due to its normal phenotype, whereas reasons for the remaining eight cases were uncertain. We also found that CMA results indicating pathogenic abnormalities further affect the rate of pregnancy termination.

Conclusions

This study showed that CMA combined with cytogenetic analysis is particularly effective in identifying sSMCs. However, in order to establish sSMC-related genotype-phenotype correlations, the inclusion of more sSMC cases will be necessary in future studies.