Single-nucleotide polymorphism array-based characterization of ring chromosome 18.

Area of Science:

• Genetics
• Human Genetics
• Chromosomal Abnormalities

Background:

• Ring chromosome 18 (r(18)) is a rare chromosomal abnormality.
• Understanding the genotype-phenotype correlation is crucial for genetic counseling and clinical management.

Purpose of the Study:

• To investigate the genotype-phenotype correlation in patients with a de novo 46,XX,r(18) karyotype.
• To identify specific genetic factors contributing to the clinical presentation of r(18).

Main Methods:

• Karyotyping and high-resolution single-nucleotide polymorphism (SNP) array analysis were performed on 9 patients with r(18).
• Parental origin investigation and detailed genotype-phenotype correlation were conducted.

Main Results:

• No recurrent breakpoints were identified for r(18).
• Additional copy number variations, including duplications in 18p and a deletion in Xp22.33 (SHOX gene), were detected in some patients.
• Clinical severity correlated with the size of deletions on chromosome 18, with distinct features associated with 18p- or 18q- deletions.

Conclusions:

• There is extensive clinical variability associated with ring chromosome 18, without a characteristic phenotype.
• The size of deletions on chromosome 18 is a key determinant of clinical severity and specific symptoms.