Abstract
Purpose::
To determine the molecular mechanism in an Axenfeld-Rieger pedigree associated with short stature (SHORT syndrome).
Methods::
A pedigree comprising 3 individuals affected by Axenfeld-Rieger syndrome, glaucoma and short stature was ascertained. Since a proportion of SHORT syndrome has been attributed to PITX2 encompassing deletions, quantitative PCR (qPCR), PITX2 sequencing, karyotyping and array comparative genome hybridization (CGH) were performed.
Results::
The patients were found to have a normal karyotype, excluding the presence of a large chromosomal anomaly. Similarly qPCR and sequencing did not identify any segmental rearrangement or mutation affecting PITX2 (4q25). Array CGH also excluded the possibility of a segmental duplication/deletion involving the known Axenfeld-Rieger loci (4q25, 6p25, 13q14 and 16q24), and identified one area of the genome with a reduced intensity hybridization signal.
Conclusions::
These data exclude the possibility of a chromosomal rearrangement involving PITX2 (4q25), FOXC1 (6p25), or the reported Axenfeld-Rieger loci (13q14 and 16q24). The breadth of the clinical phenotype is in keeping with a contiguous gene syndrome and experiments are commencing to determine whether the localized reduced hybridization signal is attributable to segmental deletion or copy number polymorphism.
Keywords: genetics • retinal development • candidate gene analysis