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Mitochondrial Dysfunction may explain symptom variation in Phelan-McDermid Syndrome
Journal article   Open access   Peer reviewed

Mitochondrial Dysfunction may explain symptom variation in Phelan-McDermid Syndrome

Richard E Frye, Devin Cox, John Slattery, Marie Tippett, Stephen Kahler, Doreen Granpeesheh, Shirish Damle, Agustin Legido and Michael J Goldenthal
Scientific reports, v 6(1), pp 19544-19544
29 Jan 2016
DOI: https://doi.org/10.1038/srep19544
PMID: 26822410
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1038/srep19544View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Adolescent Adult Autistic Disorder - genetics Case-Control Studies Child Child, Preschool Chromosome Deletion Chromosome Disorders - enzymology Chromosome Disorders - genetics Chromosome Disorders - pathology Chromosomes, Human, Pair 22 - enzymology Chromosomes, Human, Pair 22 - genetics Citrate (si)-Synthase - genetics Electron Transport - genetics Female Gene Deletion Genes, Mitochondrial Humans Male Mitochondria - pathology Registries Young Adult
Phelan-McDermid Syndrome (PMS), which is defined by a deletion within 22q13, demonstrates significant phenotypic variation. Given that six mitochondrial genes are located within 22q13, including complex I and IV genes, we hypothesize that mitochondrial complex activity abnormalities may explain phenotypic variation in PMS symptoms. Complex I, II, II + III and IV activity was measured in 51 PMS participants. Caretakers completed questionnaires and provided genetic information through the PMS foundation registry. Complex activity was abnormal in 59% of PMS participants. Abnormalities were found in complex I and IV but not complex II + III and II activity, consistent with disruption of genes within the 22q13 region. However, complex activity abnormalities were not related to specific gene deletions suggesting a "neighboring effect" of regional deletions on adjacent gene expression. A specific combination of symptoms (autism spectrum disorder, developmental regression, failure-to-thrive, exercise intolerance/fatigue) was associated with complex activity abnormalities. 64% of 106 individuals in the PMS foundation registry who did not have complex activity measured also endorsed this pattern of symptoms. These data suggest that mitochondrial abnormalities, specifically abnormalities in complex I and IV activity, may explain some phenotypic variation in PMS individuals. These results point to novel pathophysiology mechanisms and treatment targets for PMS patients.

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42 citations in Web of Science
39 citations in Scopus

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Genetics & Heredity
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