Unknown

Dataset Information

0

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.


ABSTRACT: 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.

SUBMITTER: Papachristoforou R 

PROVIDER: S-EPMC3897804 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

altmetric image

Publications

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.

Papachristoforou Rena R   Petrou Petros P PP   Sawyer Hilary H   Williams Maggie M   Drousiotou Anthi A  

JIMD reports 20130904


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 as  ...[more]

Similar Datasets

| S-EPMC4501235 | biostudies-literature
2007-11-01 | GSE4864 | GEO
| S-EPMC2613282 | biostudies-literature
| S-EPMC8930472 | biostudies-literature
| S-EPMC4236512 | biostudies-literature
| S-EPMC7140460 | biostudies-literature
| S-EPMC9541528 | biostudies-literature
| S-EPMC6606980 | biostudies-literature
| S-EPMC5081055 | biostudies-literature
2008-06-13 | E-GEOD-4864 | biostudies-arrayexpress