Mosaic tetrasomy 8p: molecular cytogenetic confirmation and measurement of glutathione reductase and tissue plasminogen activator levels.
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.
Fisher
A M
AM
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Odstock, Wiltshire, England.
Barber
J C
JC
Crolla
J A
JA
James
R S
RS
Lestas
A N
AN
Jennings
I
I
Dennis
N R
NR
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
D004276:DNA, Satellite; D005980:Glutathione Reductase; D010959:Tissue Plasminogen Activator