Molecular delineation of small supernumerary marker chromosomes using a single nucleotide polymorphism array

Area of Science:

• Genetics
• Prenatal Diagnosis
• Molecular Cytogenetics

Background:

• Establishing genotype-phenotype correlations for small supernumerary marker chromosomes (sSMCs) is crucial in prenatal diagnosis.
• Karyotyping of amniotic fluid samples is a standard prenatal diagnostic procedure.

Purpose of the Study:

• To investigate the molecular characteristics of sSMCs identified during prenatal diagnosis.
• To enhance the genotype-phenotype correlation for sSMCs using SNP array analysis.

Main Methods:

• Karyotyping of 20,481 amniotic fluid samples.
• Molecular characterization of sSMCs using single nucleotide polymorphism (SNP) array.

Main Results:

• Fifteen cases of sSMC were detected (0.073% frequency), with origins identified in 14 cases, predominantly from acrocentric chromosomes and the Y chromosome.
• Mosaicism was observed in over half of the sSMC cases (8/15), and pathogenicity was noted in 9/15 cases.
• One sSMC case with a neocentromere on chromosome 3 showed a pathogenic gain in the 3q26.31q29 region, correlating with ultrasound findings of nasal bone hypoplasia.

Conclusions:

• The clinical presentation of sSMCs is highly variable, necessitating further genetic testing and parental karyotype analysis.
• SNP array technology enables detailed characterization of sSMCs, strengthening genotype-phenotype correlations.
• Accurate characterization of sSMCs facilitates improved genetic counseling for prenatal diagnosis.