Clinical Trial: Mitochondrial Dysfunction in Phelan-McDermid Syndrome: Explaining Clinical Variation and Providing a Path Towards Treatment

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Mitochondrial Dysfunction in Phelan-McDermid Syndrome: Explaining Clinical Variation and Providing a Path Towards Treatment

Brief 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).

Detailed Summary:

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 i
Sponsor: University of Arkansas

Current Primary Outcome: Electron Transport Chain function derived from buccal cells of known PMS patients [ Time Frame: Up to two years ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University of Arkansas

Dates:
Date Received: November 25, 2013
Date Started: May 2012
Date Completion:
Last Updated: June 22, 2015
Last Verified: June 2015