De novo simultaneous reciprocal translocation and deletion

Area of Science:

• Genetics
• Human Genetics
• Cytogenetics

Background:

• Chromosomal abnormalities are a significant cause of congenital disorders.
• Translocations and deletions can lead to complex genetic conditions.
• Identifying the precise nature of chromosomal rearrangements is crucial for understanding their impact.

Observation:

• A female infant presented with severe mental retardation, hypotonicity, edema, cyanosis, heart murmur, and nystagmus.
• Karyotype analysis revealed a complex three-breakpoint translocation and deletion involving chromosomes 18 and 21: 46,XX,del(21)t(18;21)(18p-q11::21q21-qter;21pter-q11::18q11-qter).
• Both parents had normal karyotypes, indicating a de novo event in the infant.

Findings:

• The infant was monosomic for a segment of chromosome 21 (band q11-q21).
• The observed translocation was a result of a three-breakpoint exchange.
• The genetic findings provide a molecular explanation for the infant's severe developmental phenotype.

Implications:

• This case underscores the importance of detailed cytogenetic analysis in diagnosing developmental disorders, even with apparently normal parental karyotypes.
• Undetected microdeletions associated with de novo reciprocal translocations may contribute to intellectual disability.
• Further research into complex chromosomal rearrangements can improve diagnostic yield and genetic counseling for affected families.