CP+Primary+Research

In 2011 two separate studies were conducted among individuals with Cerebral Palsy. The etiology of the disease is attributed to many factors, but the specific mechanism by which the symptoms arise is fairly unclear. Genetic factors, like a deletion in the AP4E1 gene for example, are thought to result in a type of autosomal recessive CP. In this specific "form" of CP, there is no clear brain damage found, but all of the symptoms resemble those found in individuals with the common "form" of CP.
 * Overview **

** The First Study ** This first study examined the effects of genetic abnormalities in individuals with CP. A Palestinian-Jordanian family was researched because two siblings were described as being affected by a spontaneous type of CP, or one that arose with no clear damage to the brain (Moreno-De-Luca, A., et al., 2011). Both patients were born at a full term pregnancy and there were no labor/delivery issues. It was found that both had microcephaly, or small heads, and had consistent symptoms with that of CP. After performing microarray analysis, the scientists identified a deletion of chromosome 15 in both patients, including the 5' end of the adaptor related protein complex-4, epsilon-1 (AP4E1) gene (2011). After analyzing the data, the scientists provided evidence that a mutation of the AP4E1 gene may be a major factor in individuals with an autosomal recessive type of CP. The AP-complex family plays a role in mediating integral membrane protein sorting and is expressed in neurons throughout the developmental stages of one's body. The scientists proposed that disruption in any of the AP-4 subunits could contribute to the symptoms seen in the patients of this study as well as other CP patients in general.

The findings from the study provide more evidence that there are types of CP that can be caused by genetic disruptions. Specific mutation or deletion events in the AP4E1 gene were found to result in developmental brain disorders like CP (Moreno-De-Luca, A., et al., 2011).



**The Second Study** This second study examined 8 individuals from 3 related families who had intellectual disabilities and similar symptoms to individuals with CP. Pregnancies and births were normal, and there were no clinical signs of damage to any of the affected individuals' brains/nervous systems (Jamra, R. A., et al., 2011). Genetic analysis of the individuals and their families was conducted. After performing linkage analysis of DNA, the researchers found significant linkage peaks on chromosome 15 where the AP4E1 gene is found: 15q21.1-q25.1 (2011). A deletion of AP4E1 was found to be associated with the symptoms of microcephaly and intellectual disability. Other features such as epilepsy, waddling gait, and muscle deformities were observed in many of the patients with this deletion as well (2011). This study gives way to the idea that the AP4E1 deletion/mutation could enhance the symptoms in someone with CP, or contribute to some of the secondary effects seen.

This second study also provides more evidence that there exists a type of autosomal recessive CP caused by disruptions in the AP4E1 gene. The individuals examined during this study had symptoms consistent with those found in CP. Finally, it further supports the hypothesis that the AP-4 family plays a crucial role in brain development and function because disruption of this family, and more specifically the AP4E1 gene, results in a variety of intellectual disorders including CP (Jamra, R. A., et al., 2011).



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