The emerging microduplication 3q13.31: Expanding the genotype-phenotype correlations of the reciprocal microdeletion...

Area of Science:

• Genetics
• Developmental Biology
• Human Pathology

Background:

• Microdeletion and microduplication syndromes are recognized causes of developmental delay and congenital malformations.
• A recently identified 3q13.31 microdeletion syndrome presents with developmental delay, postnatal overgrowth, and dysmorphic features.
• The reciprocal microduplication at 3q13.31 has been less characterized, with limited case reports.

Observation:

• This study reports a female infant with a 3.34 Mb microduplication of the 3q13.2q13.31 region inherited from her mother.
• The infant exhibited severe intellectual disability, learning difficulties, intrauterine and postnatal growth retardation, and skeletal abnormalities, but no dysmorphic traits.
• The microduplication spans the shortest region of overlap, including genes DRD3, ZNF80, TIGIT, MIR568, and ZBTB20.

Findings:

• The observed phenotype in the infant aligns with known microduplication syndromes and the 3q13.31 microdeletion syndrome.
• DRD3 and ZBTB20 are identified as strong candidate genes contributing to the neurodevelopmental defects and growth retardation seen in this microduplication.
• The rearrangement mechanism may involve nonallelic homologous recombination mediated by human endogenous retrovirus elements.

Implications:

• This case expands the clinical understanding of 3q13.2q13.31 microduplications, particularly the absence of dysmorphic features in this instance.
• The identification of candidate genes provides insights into the genetic underpinnings of neurodevelopmental and growth disorders associated with this chromosomal region.
• Further research into the mechanisms of such rearrangements can aid in diagnosing and potentially managing these complex genetic conditions.