Uniparental Disomy

The most common explanation for uniparental disomy is trisomy “rescue” due to chromosome nondisjunction in cells of a trisomic conceptus to restore a disomic state. The cause of the originating trisomy is typical meiotic nondisjunction in one of the parental germlines; the rescue results from a second nondisjunction event, this one occurring mitotically at an early postzygotic stage, thus “rescuing” a fetus that otherwise would most likely be aborted spontaneously (the most common fate for any trisomic fetus; see Table 5-2). Depending on the stage and parent of the original nondisjunction event (i.e., maternal or paternal meiosis I or II), the location of meiotic recombination events, and which chromosome is subsequently lost in the postzygotic mitotic nondisjunction event, the resulting fetus or liveborn can have complete or partial isodisomy or heterodisomy for the relevant chromosome.

Although it is not known how common uniparental disomy is overall, it has been documented for most chromosomes in the karyotype by demonstrating uniparental inheritance of polymorphisms in a family. Clinical abnormalities, however, have been demonstrated for only some of these, typically in cases when an imprinted region is present in two copies from one parent (see the section on genomic imprinting later in this chapter) or when a typically recessive condition (which would ordinarily imply that both parents are obligate carriers; see Chapter 7) is observed in a patient who has only one documented carrier parent. It is important to stress that, although such conditions frequently come to clinical attention because of mutations in individual genes or in imprinted regions, the underlying pathogenomic mechanism in cases of uniparental disomy is abnormal chromosome segregation.

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Nov 27, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Disomy

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