X-Y translocations

Epidemiology and Etiology:

· Classical X-Y translocation:

· Majority are familial

· Arises during spermatogenesis following a reciprocal exchange between X and Y

· Homology between Kallmann locus on the X chromosome and a Kallman-like nonfunctional pseudogene on Yq

· Only females are capable of passing it on to progeny

· 46,X,der(X)t(X;Y)(p22.3;q11)

· 46,Y,der(X)t(X;Y)(p22.3;q11)

· Resulting Xp deletion

· Other X-Y translocations are typically de novo

· Cryptic Xp-Yp translocation

· Arises during paternal meiosis

· Always sporadic (affected males are invariably infertile)

· NAHR - Recombination between homologous PRKX and PRKY genes on Xp and Yp

· Leads to the formation of both XX amles and XY females

· Appears to occur preferentially in association with a Yp inversion polymorphism

·

· Dicentric X-Y

· Distal Yp breakpoint and distal Xp or Xq breakpoint

· der(X) chromosomes from translocations of varying lengths of Yq to a breakpoint at various levels on Xp or Xq

· der(Y) chromosomes from breakpoints at Xp and Yq

· Xq-Yq exchange

· NAHR:

· Recombination between homologous PRKX and PRKY genes on Xp and Yp

· Leads to the formation of both XX amles and XY females

· Appears to occur preferentially in association with a Yp inversion polymorphism

· Homology between Kallmann locus on the X chromosome and a Kallman-like nonfunctional pseudogene on Yq

·

Common sites:

·

Gross features:

· Classical X-Y translocation:

· Xp deletion features

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

· Homology between Kallmann locus on the X chromosome and a Kallman-like nonfunctional pseudogene on Yq

· X-inactivation in 46,X,der(X)t(X;Y)(p22.3;q11)

· tends toward inactivation of the der(X)

· but it is variable and unpredictable

· MLS gene may be disrupted or aberrantly inactivated

· Microophthalmia with linear skin defects

· SRY may be lost

· Female sexual development

· Cryptic Xp-Yp translocation

· Usually not visible

· 46,XX male or 45,X male

· Xq-Yq exchange

· Apparent Yq deletion

· Actually contains a very small segment of distal Xq

Other features:

· Male carrier is almost invariably infertile

· 46,X,der(X)t(X;Y)(p22.3;q11)

· Female

· Fertile

· Normal intelligence

· 50% risk of passing on translocation (son or daughter)

· 46,Y,der(X)t(X;Y)(p22.3;q11)

· Male

· Mental impairment usually (more likely in proximal breakpoint including MRX)

· Infertile (almost invariably)

· Spermatogenic arrest

· Cryptic Xp-Yp translocation

· Sex reversal (XX male, X male)

· Affected males are invariably infertile

· Other X-Y translocations:

· Infertility

· Intellectual defect in some

References:

· Gersen SL, Keagle MB. The Principles of Clinical Cytogenetics. 2nd ed. Humana Press; 2004:616.