1q21.1 microduplication in a patient with mental impairment and congenital heart defect

Area of Science:

• Genetics
• Developmental Biology
• Pediatrics

Background:

• 1q21.1 duplication is a rare copy number variant associated with congenital malformations.
• These malformations can include developmental delay, autism spectrum disorder, dysmorphic features, and congenital heart anomalies.

Observation:

• A Chinese female patient presented with multiple congenital malformations, including congenital heart defect, mental impairment, and developmental delay.
• Her parents and monozygotic twin sister were phenotypically normal.
• High-resolution genome-wide single nucleotide polymorphism array identified a 1.6 Mb duplication in the 1q21.1 chromosomal region.

Findings:

• The identified 1.6 Mb duplication in chromosome region 1q21.1 was absent in the patient's parents and twin sister, suggesting a de novo occurrence.
• The duplicated region encompasses the HFE2 gene, implicated in hereditary hemochromatosis.
• This case represents the first reported instance of 1q21.1 duplication in mainland China.

Implications:

• This case expands the understanding of 1q21.1 duplication syndrome's phenotypic variability.
• It underscores the importance of genetic testing for undiagnosed congenital anomalies, even in the presence of normal parental phenotypes.
• The findings contribute to the genetic landscape of copy number variants in the Chinese population.