Coexisting Conditions Modifying Phenotypes of Patients with 22q11.2 Deletion Syndrome.

Area of Science:

• Genetics
• Genomic Medicine
• Clinical Genetics

Background:

• 22q11.2 deletion syndrome (22q11.2DS) is a common genomic disorder with a wide range of clinical manifestations.
• The contribution of additional genetic variants to the phenotypic variability in 22q11.2DS is not fully understood.

Purpose of the Study:

• To investigate the frequency and impact of additional genomic variants in patients diagnosed with 22q11.2DS.
• To determine if genome-wide diagnostic methods can uncover clinically relevant findings beyond the primary deletion.

Main Methods:

• Microarray analysis was performed on 159 patients (82 prenatal, 77 postnatal) with 22q11.2DS.
• Exome sequencing was conducted on 86 postnatal patients with 22q11.2DS.

Main Results:

• Microarray identified 10 additional copy number variants (CNVs) outside the 22q11.2 region in 6.3% of cases, suggesting a contribution to clinical presentation.
• Exome sequencing revealed 3 pathogenic and 5 likely pathogenic single nucleotide variants (SNVs) and small CNVs in 3.49% and 5.81% of patients, respectively.

Conclusions:

• Genome-wide diagnostic approaches, including microarray and exome sequencing, are valuable for identifying additional clinically relevant genetic alterations in 22q11.2DS patients.
• These findings highlight the importance of considering secondary genetic variations in understanding the broad phenotypic spectrum of 22q11.2DS.