Fifty probands with extra structurally abnormal chromosomes characterized by fluorescence in situ hybridization

Area of Science:

• Genetics
• Cytogenetics
• Molecular Biology

Background:

• Extra structurally abnormal chromosomes (ESACs) are frequently observed in individuals with developmental abnormalities and malformations.
• Understanding the specific characteristics and origins of ESACs is crucial for predicting associated clinical outcomes.

Purpose of the Study:

• To characterize 50 probands with ESACs using advanced molecular techniques.
• To correlate specific ESAC types and sizes with clinical phenotypes and developmental outcomes.

Main Methods:

• Fluorescence in situ hybridization (FISH) with centromere-specific probes and chromosome-specific libraries.
• Construction of ESAC-specific libraries via flow sorting and degenerate oligonucleotide-primed PCR (DOP-PCR).
• Analysis of chromosome regions involved in ESACs.

Main Results:

• Twenty-three of 50 ESACs were identified as inverted duplications of chromosome 15 [inv dup(15)].
• Large inv dup(15) encompassing the Prader-Willi region were associated with a high risk of abnormalities, unlike smaller inv dup(15) not including this region.
• ESACs from chromosomes 13 or 21 showed low risk; chromosome 14 and 22 ESACs had variable risks, with one chromosome 22 ESAC showing cat eye syndrome-like anomalies.
• Small extra ring chromosomes and ESACs of i(12p) or i(18p) were linked to high abnormality risk.

Conclusions:

• The size and specific chromosomal origin of ESACs are critical determinants of associated clinical risks.
• Inv dup(15) size is a key factor in predicting phenotype, with large ones posing a significant risk.
• Certain ESACs, such as i(12p) and i(18p), consistently indicate a high risk for developmental abnormalities.