Small supernumerary marker chromosomes derived from human chromosome 11

Area of Science:

• Cytogenomics
• Human Genetics
• Rare Chromosomal Disorders

Background:

• Small supernumerary marker chromosomes (sSMC) are rare, with chromosome 11-derived sSMCs (sSMC(11)) being exceptionally infrequent.
• Only 39 cases of sSMC(11) have been previously reported in the literature.

Purpose of the Study:

• To review and expand the case data for sSMC(11).
• To delineate the critical genomic regions associated with clinical phenotypes in sSMC(11) carriers.
• To identify diagnostic and prognostic challenges in managing sSMC(11).

Main Methods:

• Comprehensive literature review of sSMC(11) cases.
• Inclusion of 18 new unpublished cases.
• Analysis of eight 'centromere-near partial trisomy 11' cases and four DECIPHER cases.

Main Results:

• Defined pericentric region borders for chromosome 11 short (p) and long (q) arms associated with clinical symptoms (2.63 Mb and 0.96 Mb, respectively).
• Narrowed the minimal pericentric region of chromosome 11 without triplo-sensitive genes to 47.68–60.52 Mb (GRCh37).
• Observed differences in clinical presentation based on the chromosomal arm involved in partial trisomy, though overlap exists.

Conclusions:

• sSMC(11) presents diagnostic and prognostic challenges, particularly in prenatal settings.
• Uniparental disomy (UPD) of chromosome 11 should be considered in sSMC(11) carrier evaluation due to potential imprinting effects.
• Further research is needed due to the low number of informative cases and overlapping phenotypes.