Paracentric Inversions

inv(X)

Epidemiology and Etiology:

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Common sites:

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Gross features:

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Histologic features:

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Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

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Other features:

· Generally innocuous

· Note that insertions may be mistaken for small inversions

· Insertions have a high genetic risk

· Parent with a paracentric inversion:

· Risk of unbalanced liveborn child:

· The vast majority of paracentric inversions are likely to be harmless

· Even when the recombinant / reunion product is theoretically viable

· Note that sex chromosomes warrant separate attention

· Inversions on record with a demonstrated recombinant:

· Inv(9)(p13p24)

· Inv(9)(q22.1q34.3)

· Inv(14)(q24.2q32.3)

· Inv(17)(p11.2p13)

· Inv(18)(q12.1q23)

· Inv(18)(q21.1q22.3)

· Inversions with breakpoints near known disease sites may warrant investigation

· Distal 11p (BWS)

· Proximal 15q (PW/AS)

· 17p13 (SMS)

· Mechanisms of unbalanced zygote:

· Recombinant gametes are generally unviable

· Dicentric product is classically unstable

· Rare cases of deletion of segment distal to inversion and duplication of small part proximal to it

· But rarely, centromere suppression could render the dicentric chromosome stable

· Tends to occur only in large inversions involving most or almost all of a long arm, with the short arms being genetically small

· “U-loop” recombination (“reunion”):

· Mutational event where the crossover within the inversion loob reverses upon itself as a U-loop

· 2 recombinant (“reunitant”) products:

· Duplication of that part of the inversion loop proximal to the crossover and deletion of that part distal to it

· Reverse of above

· Chromatid breakage with abnormal reunion at one of the entry points to the inversion loop:

· A duplication alone or a deletion alone

· Inherited paracentric inversion:

· “Very slight” risk of abnormality with a normal parental phenotype

· Subtle duplications or deletions resulting from rearrangement within or at the extremities of the inversion segment

· Inversions with breakpoints near known disease sites may warrant investigation

· Distal 11p (BWS)

· Proximal 15q (PW/AS)

· 17p13 (SMS)

· De novo paracentric inversion:

· Risk of Mendelian loci disrupted by rearrangement

· Position effect

· Epigenetic influence

· Direct disruption

· Inversions with breakpoints near known disease sites may warrant investigation

· Distal 11p (BWS)

· Proximal 15q (PW/AS)

· 17p13 (SMS)

References:

· Gardner RJM, Sutherland GR. Chromosome abnormalities and genetic counseling. Oxford University Press; 2004.