Objective The characterization of a novel large deletion in the galactose-1-phosphate uridyltransferase (GALT) gene accounting for the majority of disease alleles in Cypriot patients with classic galactosemia. Methods DNA sequencing was used to identify the mutations followed by multiplex ligation-dependent probe amplification (MLPA) analysis in the cases suspected of harboring a deletion. In order to map the breakpoints of the novel deletion, a PCR walking approach was employed. A simple PCR assay was validated for diagnostic testing for the new deletion. Haplotype analysis was performed using microsatellite markers in the chromosomal region 9p. RT-PCR was used to study RNA expression in lymphoblastoid cell lines. Results The new deletion spans a region of 8489 bp and eliminates all GALT exons as well as the non-translated sequences of the adjacent interleukin 11 receptor alpha (IL11RA) gene. In addition, the deletion is flanked by a 6 bp block of homologous sequence on either side suggesting that a single deletion event has occurred, probably mediated by a recombination mechanism. Microsatellite marker analysis revealed the existence of a common haplotype. The RNA expression studies showed a lack of IL11RA transcripts in patients homozygous for the deletion. Conclusions We have identified and characterized a novel contiguous deletion which affects both the GALT enzyme and the IL11RA protein resulting in classic galactosemia with additional phenotypic abnormalities such as craniosynostosis, a feature that has been associated with defects in the IL11RA gene.
CITATION STYLE
Papachristoforou, R., Petrou, P. P., Sawyer, H., Williams, M., & Drousiotou, A. (2014). A novel large deletion encompassing the whole of the galactose-1-phosphate uridyltransferase (GALT) gene and extending into the adjacent interleukin 11 receptor alpha (IL11RA) gene causes classic galactosemia associated with additional phenotypic abnormalities. In JIMD Reports (Vol. 12, pp. 91–98). Springer. https://doi.org/10.1007/8904_2013_249
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