title: Partial tetrasomy 14 associated with multiple malformations.
abstract: We report on an 8-year-old female patient with multiple malformations including bilateral cleft lip and palate, coloboma, and craniosynostosis. She presented with severe intellectual disability, seizures, and gastrointestinal dysfunction. Mitochondrial investigations in a muscle biopsy revealed reduced activity in complex I of the mitochondrial respiratory chain. Chromosome analysis and fluorescent in situ hybridization (FISH) studies showed an isodicentric marker chromosome 14 that was identified in all cells analyzed in peripheral blood lymphocytes and cultured fibroblasts. Parental chromosome studies were normal. To further characterize the marker chromosome and determine its origin, we performed array-based comparative genomic hybridization (CGH) and polymorphic marker analysis with quantitative fluorescent PCR (QF-PCR). The combined results from cytogenetic and array-CGH analyses showed tetrasomy 14p13q13.1 and results from the QF-PCR point to formation of the marker chromosome in the maternal meiosis. Isodicentric chromosomes involving partial 14q have previously been reported in four cases; however, this is the first patient with tetrasomy 14p13q13.1 in non-mosaic form surviving beyond infancy.
authors.affiliation: Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. johanna.winberg@ki.se
authors.forename: Johanna
authors.initials: J
authors.lastname: Winberg
authors.forename: Kristina
authors.initials: K
authors.lastname: Lagerstedt Robinson
authors.forename: Karin
authors.initials: K
authors.lastname: Naess
authors.forename: Nicole
authors.initials: N
authors.lastname: Lesko
authors.forename: Rolf
authors.initials: R
authors.lastname: Wibom
authors.forename: Agne
authors.initials: A
authors.lastname: Liedén
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Anderlid
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordenskjöld
authors.forename: Ann
authors.initials: A
authors.lastname: Nordgren
authors.forename: Peter
authors.initials: P
authors.lastname: Gustavsson
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics; D003103:Coloboma / Q000235:genetics; D055028:Comparative Genomic Hybridization; D003398:Craniosynostoses / Q000235:genetics; D042967:Electron Transport Complex I / Q000172:deficiency / Q000378:metabolism; D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics; D007621:Karyotyping; D018895:Microsatellite Repeats / Q000235:genetics; D028361:Mitochondrial Diseases / Q000378:metabolism; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000378:metabolism; D012640:Seizures / Q000235:genetics; D013548:Sweden; D058670:Tetrasomy / Q000235:genetics*
chemical_list: D042967:Electron Transport Complex I