Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02000167 |
| Other study ID # |
136271 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 2012 |
| Est. completion date |
May 2015 |
Study information
| Verified date |
June 2015 |
| Source |
University of Arkansas |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The purpose of this study is to determine whether a relationship exists between gene
deletion(s) specific to the mitochondrial electron transport chain and presentation of
clinical characteristics in patients with Phelan-McDermid Syndrome (PMS).
Description:
Phelan-McDermid Syndrome (PMS) results from a deletion within the 22q13 chromosome region.
Most children have specific physical morphology and developmental delays with many displaying
characteristics of autism spectrum disorder (ASD) including abnormalities in social
development. The behavioral aspect of PMS that parallels ASD has raised particular interest
as the SHANK3 gene, which lies in the 22q13 region, is important for synaptic development,
and animal SHANK3 knockout models demonstrate ASD characteristics thereby confirming the
importance of this gene in PMS. However, despite the importance of the SHANK3 gene,
individuals with PMS have variations in their development, behavior and medical
characteristics that cannot be fully explained by the SHANK3 deletion.
Recently, Frye (2012) has noted the existence of 6 mitochondrial genes that lie slightly
proximal to the SHANK3 gene within the 22q13 region. These include genes important electron
transport change function (SCO2, NDUFA6), mitochondrial DNA (TYMP) and RNA (TRMU) metabolism,
fatty acid metabolism (CPT1B) and tricarboxylic acid cycle function (ACO2). Since most
Individuals with PMS have deletions that include chromosomal deletion outside of the SHANK3
region, it is very likely that many, if not most, of children with PMS may have deletions in
these mitochondrial genes. Many of these genes have been linked to mitochondrial disease,
even in the heterozygous state. Even if recognized, mitochondrial disease is only linked to a
homozygous abnormal state (autosomal recessive), the loss of one gene (heterozygous state)
could result in symptomatology when associated with deletions in other mitochondrial or
non-mitochondrial genes. Abnormalities in mitochondrial pathways can result in neurologic and
non-neurologic symptoms including those sometimes seen in children with PMS. Added with the
SHANK3 deletion, abnormalities in these mitochondrial genes could explain variations in
patterns of development and the eventual cognitive potential.
References: Frye RE. Mitochondrial disease in 22q13 duplication syndrome. J Child Neurol.
2012; 27(7):942-9.
