Maternal complex chromosomal rearrangement leads to TCF12 microdeletion in a patient presenting with coronal...

Area of Science:

• Genetics and Genomics
• Developmental Biology
• Clinical Medicine

Background:

• Intellectual disability and craniofacial malformations can arise from complex genetic rearrangements.
• Standard karyotyping may identify apparently balanced translocations, but often misses submicroscopic deletions.
• Chromosomal abnormalities involving chromosome 15 can lead to developmental disorders.

Observation:

• A young child presented with intellectual disability and unilateral coronal craniosynostosis.
• Maternal karyotype revealed an apparently balanced translocation between chromosomes 2 and 15 [t(2;15)(q21;q21.3)].
• The child had a de novo deletion on chromosome 15 (15q21.3q22.2) and a complex maternal chromosomal rearrangement.

Findings:

• Array comparative genomic hybridization (array-CGH) detected a 3.64 Mb de novo deletion on chromosome 15.
• This deletion resulted in haploinsufficiency of the TCF12 gene, explaining the coronal craniosynostosis.
• Fluorescence in situ hybridization (FISH) analysis elucidated a complex maternal rearrangement involving translocation and insertion, leading to the deletion via meiotic recombination.

Implications:

• This case highlights the utility of array-CGH in detecting microdeletions associated with apparently balanced rearrangements.
• FISH analysis is crucial for precisely identifying the chromosomal mechanisms underlying genomic imbalances.
• Understanding these complex rearrangements is vital for accurate genetic counseling and diagnosis of developmental disorders.