Duplications

dup(Xp)

dup(Xq)

dup(3)(q?26.3)

dup(8p)

dup(11)(p15.5)pat - BWS

i(12)(p10) – Pallister-Killian

dup(15)(q11.2)

psu idic(15)(q13)

dup(17)(p11.2p11.2)

dup(17)(p12p12) – Charcot-Marie-Tooth

dup(22)(q11.2q11.2)

psu idic(22)(q11.2)

Epidemiology and Etiology:

• Tandem duplication:
• Original and duplicated segments ordered in tandem fashion
• May be direct or inverted
• Mechanisms of recurrent tandem duplications:
• Non-allelic homologous recombination (NAHR):
• Paralogous DNA sequences misaligning during meiosis
• Non-allelic sister chromatid exchange
• Same process occurring between sister chromatids
• During meiosis or mitosis
• May result in mosaicism if during post-zygotic mitosis
• U-loop reunion following a two-strand break in a telomeric segment
• Results in an inverted duplication accompanied by a deletion of the terminal segment
• Chromosome 8p commonly involved
• M=F parental origins
• Additional material from another chromosome:
• Non-allelic homologous recombination between region of homology or near-homology in two different chromosomes
• Single segment exchange during meiosis
• Asymmetric segregation resulting in a duplication of the material on the derivative chromosome (the same mechanism could give rise to a deletion
• Genes with tandemly arranged homologous sequences that tend to give rise to duplication mutations:
• LDLR (Alu repeats) (Familial hypercholesterolemia)

Common sites:

Gross features:

Histologic features:

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

Other features:

References:

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