15q11.2-13 duplication, mitochondrial dysfunction, and developmental disorders.
Multiple developmental phenotypes have been associated with duplication in the 15q11-13 region. Recently, the 15q11-13 duplication has been associated with a distinct pattern of mitochondrial abnormalities that includes a deficiency in complex III. This report describes the third case with this duplication and a similar pattern of mitochondrial dysfunction. Genetic studies performed on this case rule out the previously suggested role of the UBE3A gene. It is proposed that interactions of the duplicated SNRPN gene with nuclear respiratory factor 1 could result in destabilization of mitochondrial complex formation and activation of apoptosis under metabolic stress, resulting in the pattern of abnormalities found in the current and previously reported cases. In light of the frequency of this duplication in children with developmental dishabilles, the wider implication of the association between this duplication and mitochondrial dysfunction needs to be considered.
Frye
Richard E
RE
Department of Pediatrics and Neurology, Division of Child and Adolescent Neurology, University of Texas Health Science Center, Houston, Texas, USA. Richard.E.Frye@uth.tmc.edu
D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002884:Chromosomes, Human, Pair 15; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055517:snRNP Core Proteins / Q000235:genetics
D051266:Nuclear Respiratory Factor 1; C526417:SNRPN protein, human; D055517:snRNP Core Proteins; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases