title: Mosaic tetrasomy 8p: molecular cytogenetic confirmation and measurement of glutathione reductase and tissue plasminogen activator levels.
abstract: We report the case of a 5-year-old girl with severe developmental disabilities, skeletal anomalies, hypotonia, rectal atresia, malrotation of the intestine, horseshoe kidney, vesicoureteric reflux, and minor facial anomalies. Conventional cytogenetic techniques suggested that she had a mosaic 46,XX/47,XX,+i(8p) constitution, and the identity of the isochromosome was confirmed by in situ hybridization and chromosome painting. Polymorphic DNA markers are consistent with the i(8p) having arisen as the result of a segregation error and centromere misdivision at the second maternal meiotic division. The i(8p) was seen in 17/25 (68%) lymphocytes at the age of one month but had declined to 31/100 (31%) cells by the age of 5 years. At this time the i(8p) was seen in 30/68 (44%) cultured skin fibroblasts. The proposita had an approximately twofold increase in red cell glutathione reductase activity but a normal level of tissue-plasminogen activator. These enzyme results are consistent with the known localisation of the glutathione reductase gene on the short arm of chromosome 8 but suggest that the tissue-plasminogen activator gene may map outside this region.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Odstock, Wiltshire, England.
authors.forename: A M
authors.initials: AM
authors.lastname: Fisher
authors.forename: J C
authors.initials: JC
authors.lastname: Barber
authors.forename: J A
authors.initials: JA
authors.lastname: Crolla
authors.forename: R S
authors.initials: RS
authors.lastname: James
authors.forename: A N
authors.initials: AN
authors.lastname: Lestas
authors.forename: I
authors.initials: I
authors.lastname: Jennings
authors.forename: N R
authors.initials: NR
authors.lastname: Dennis
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002503:Centromere; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D025063:Chromosome Disorders; D002898:Chromosomes, Human, Pair 8; D004276:DNA, Satellite / Q000032:analysis; D005260:Female; D005980:Glutathione Reductase / Q000097:blood / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D009030:Mosaicism; D009035:Mothers; D009630:Nondisjunction, Genetic; D016133:Polymerase Chain Reaction; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D004276:DNA, Satellite; D005980:Glutathione Reductase; D010959:Tissue Plasminogen Activator