Duplication of chromosome region 8p23.1 ? p23.3: A benign variant?

Abstract

Chromosome analysis was performed in a 34-year-old man who was phenotypically normal except for oligoasthenozoospermia. In this patient, analysis of GTG-banded chromosomes showed in one chromosome 8 additional chromosomal material of unknown origin. To characterize the aberrant chromosome more precisely, a paint specific for chromosome region 8pter-->8p23.1 was generated by microdissection and degenerated oligonucleotide primed-polymerase chain reaction (DOP-PCR) and used as fluorescence in situ hybridization (FISH) paint. After reverse painting, hybridization signals were only found on the short arm of the two chromosomes 8, with an enlarged signal on the derivative chromosome 8. The duplication was characterized further with band-specific FISH probes. We concluded that (part of) chromosome region 8p23.1-->p23.3 was duplicated. Chromosome analysis of the parents showed that the dup(8) was of maternal origin and that the fertile brother of the index patient also was a carrier of the chromosome aberration. There was no history of miscarriages. We suggest that duplication of region 8p23.1-->p23.3 can be regarded as euchromatic variant or duplication with no phenotypic effect.

Duplications and copy number variants of 8p23.1 are cytogenetically indistinguishable but distinct at the molecular level

“…Thirdly, overlapping duplications of 8p22 -p23.1 have been reported in patients with Kabuki syndrome 15 but these findings have not been replicated by others in clinically well characterised patients. 16 Fourthly, duplications of 8p23.1 -8p23.3 have been reported in normal individuals 17,18 and it is therefore possible that the clinical effect of the smaller triplication in family 1 is minimal. Many of these duplications include the GATA4 gene, deletions 19 and intragenic mutations of which give rise to heart disease.…”

Failure to detect an 8p22–8p23.1 duplication in patients with Kabuki (Niikawa–Kuroki) syndrome

“…In most cases this duplication was believed to be a benign variant with no phenotypic effect 12 and described as an euchromatic variant (EV). 13,14 This was disputed by Tsai et al 15 who reported on 12 patients with an 8p23 duplication and a significant phenotype comprising mainly heart defects.…”

Genome-wide screening using array-CGH does not reveal microdeletions/microduplications in children with Kabuki syndrome

“…15 Imbalances of the 8p region have been frequently reported with a wide range of different phenotypes, and also in individuals without clinical manifestations. 16,17 The duplication reported by…”