Distal 22q11.2 microduplication encompassing the BCR gene

Area of Science:

• Genetics
• Human Genetics
• Genomic Medicine

Background:

• Chromosome 22 band q11.2 is prone to microdeletions and microduplications due to low copy repeats (LCRs).
• LCRs mediate non-allelic homologous recombination (NAHR), causing recurrent chromosomal rearrangements.
• The telomeric LCRs at 22q11.2 are implicated in a newly recognized distal 22q11.2 microdeletion syndrome.

Observation:

• A 4.5-year-old girl presented with failure to thrive, developmental delay, and relative macrocephaly.
• She inherited a ~2.1 Mb microduplication at distal 22q11.2 from her father.
• This microduplication spans ~34 genes and is flanked by telomeric 22q11.2 LCRs.

Findings:

• The telomeric LCRs at distal 22q11.2 can mediate both microdeletions and microduplications.
• The patient's microduplication is associated with subtle clinical features.

Implications:

• Both deletions and duplications in this distal 22q11.2 region result in similar subtle clinical features.
• These include mild to moderate intellectual disability, developmental delay, and mild dysmorphic features.
• Understanding LCR-mediated rearrangements is crucial for diagnosing and managing 22q11.2 disorders.