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

This study has been completed.
St. Christopher's Hospital for Children
Information provided by (Responsible Party):
University of Arkansas Identifier:
First received: November 25, 2013
Last updated: June 22, 2015
Last verified: June 2015
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).

Phelan-McDermid Syndrome

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Mitochondrial Dysfunction in Phelan-McDermid Syndrome: Explaining Clinical Variation and Providing a Path Towards Treatment

Resource links provided by NLM:

Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • Electron Transport Chain function derived from buccal cells of known PMS patients [ Time Frame: Up to two years ]
    Electron transport chain (ETC) function will be measured in cells collected using Buccal swabs to determine if certain PMS patients symptomatology and clinical characteristics/variations can be explained due to variations in patterns of ETC function in this cohort

Enrollment: 51
Study Start Date: May 2012
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Phelan-McDermid Syndrome only
Diagnosed with Phelan-McDermid Syndrome; 50 subjects to be recruited. 1-21 years of age
Co-morbid Phelan-McDermid Syndrome & Mitochodrial Disorder
1-21 years of age; Diagnosed with Phelan-McDermid Syndrome AND diagnosed with Mitochondrial Disorder; 50 subjects to be recruited.

Detailed 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.


Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients will be identified through the registry for this specific aim. PMS patients in the registry will be offered to be entered the study.

Inclusion Criteria:

  • 1-21 years of age
  • Diagnosed with Phelan-McDermid Syndrome AND diagnosed with Mitochondrial Disorder
  • Diagnosed with Phelan-McDermid Syndrome

Exclusion Criteria:

  Contacts and Locations
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Please refer to this study by its identifier: NCT02000167

United States, Arkansas
Arkansas Children's Hospital Research Institute
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
University of Arkansas
St. Christopher's Hospital for Children
Principal Investigator: Richard E Frye, M.D./Ph.D. University of Arkansas for Medical Sciences; Arkansas Children's Hospital Research Institute
Principal Investigator: Michael J Goldenthal, Ph.D. Drexel University College of Medicine
  More Information

Additional Information:
Responsible Party: University of Arkansas Identifier: NCT02000167     History of Changes
Other Study ID Numbers: IRB# 136271
Study First Received: November 25, 2013
Last Updated: June 22, 2015

Keywords provided by University of Arkansas:
Electron Transport Chain
Mitochondrial Disease
Chromosomal Deletion

Additional relevant MeSH terms:
Chromosome Deletion
Chromosome Disorders
Pathologic Processes
Chromosome Aberrations
Congenital Abnormalities
Genetic Diseases, Inborn processed this record on May 24, 2017