Osteogénesis Imperfecta (OI)

naturaleza frágil, espíritu inquebrantable

Asociación Nacional Huesos de Cristal

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Qué es la OI
Diagnostic and manifestations
Qué es una fractura
Prediction and incidence
Herencia y mosaicismo
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Inheritance and Mosaicism

The OI presents dominant genetic inheritance, which means that when one parent has OI, every newborn child has a 50% chance of being affected equally.
Other times, the IO is not inherited, but is caused by a mutation. In this case, neither parent shows no sign of OI. The mutation is again dominant inheritance.

And a particularly complicated is the possibility of mosaicism.
Because of all this complexity, it is recommended to seek genetic counseling staff.

The Osteogenesis Imperfecta (OI) is a disease of genetic type, and therefore is hereditary. Types I and IV sometimes appear in families over several generations. The kind of inheritance is dominant: a parent or medre affected has a 50% chance of transmitting the altered gene to each child, and another 50% to transmit the gene-altered (all of us have two copies of each gene, except for the genes linked to the chromosomes that carry the legacy sex).

Although there is some degree of variation between affected family members (eg number of fractures), the clinical classification of the disease in each affected family is generally the same throughout the generations, as it is the same genetic defect that passed on from father to son.

Moreover, the O.I. Is a very heterogeneous among cases without family relationship: the individual case may be a genetic defect in different genes that carry the information of collagen.

The RO, like other dominant genetic diseases may occur spontaneously. This is particularly true in types II and III, which are typically more severe forms of OI, but it may occur in other cases. When a child is born / a parent is not affected because it usually has appeared a mutation in a gene of collagen. Mutations are sporadic and unpredictable changes in the genetic information carried by DNA. It is most likely that the mutation occurred in one of the two gametes (egg or sperm), whose union leads the child to affected / a.

In those families in which appears a case of spontaneous OI The siblings unaffected citizens are not carriers of the mutation, therefore, the children of those do not have a particular genetic risk of having the disease, by contrast, a child affected is a student with a probability of 50% convey the mutant gene, and thus the disease to their own children, starting a new chain of genetic inheritance, with 50% probability, over new generations.

With regard to the parents, studies in a large number of families with children born with OI type II (lethal) parents not affected, it has shown a certain recurrence of the disease (ie, new children with OI) , in a 5 to 7% of cases.

This strange situation was explained wrongly long with a different type of genetic inheritance (autosomal recessive), and even today can lead to confusion (and therefore, a genetic counseling wrong) to physicians who are not fully up to date in terms to new research on the IO Peter Byers and his colleagues at the University of Seattle, USA, and subsequently many other researchers have shown that the recurrence of cases of OI Families with no previous cases of this disease is caused by mutations in one of the dominant genes of collagen (COL1A1 and COL1A2): spontaneous mutation, rather than affect a single cigoto (egg or sperm), has affected a certain portion of them in the parent, who, therefore, has a certain probability of breed more than one child affected by the disease.

This phenomenon is called mosaicism.

It is very difficult to diagnose cases of mosaicism: find the mutation in their cells could be worse than find the needle in the haystack. Only after the mutation has been identified in the child / concerned / a, which the carrier in all its cells, it is possible to design molecular analysis to try to seek mosaicism in parents (usually in ova and / or sperm, and also in the white blood cells), and then, try to estimate the theoretical probability of repeat child with OI.

The mosaicism may occur in any type of OI, but so far has only been documented for more severe types of the disease (type II), and their frequency has been experimentally estimated between 5 and 7%.




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