Publication
Alu-Alu Recombination Underlying the First Large Genomic Deletion in GlcNAc-Phosphotransferase Alpha/Beta (GNPTAB) Gene in a MLII Alpha/Beta Patient
| dc.contributor.author | Coutinho, Maria Francisca | |
| dc.contributor.author | da Silva Santos, Liliana | |
| dc.contributor.author | Lacerda, Lúcia | |
| dc.contributor.author | Quental, Sofia | |
| dc.contributor.author | Wibrand, F. | |
| dc.contributor.author | Lund, A.M. | |
| dc.contributor.author | Johansen, K.B. | |
| dc.contributor.author | Prata, Maria João | |
| dc.contributor.author | Alves, Sandra | |
| dc.date.accessioned | 2013-03-21T16:05:50Z | |
| dc.date.available | 2013-03-21T16:05:50Z | |
| dc.date.issued | 2012-04 | |
| dc.description.abstract | Mucolipidosis type II α/β is a severe, autosomal recessive lysosomal storage disorder, caused by a defect in the GNPTAB gene that codes for the α/β subunits of the GlcNAc-phosphotransferase. To date, over 100 different mutations have been identified in MLII α/β patients, but no large deletions have been reported. Here we present the first case of a large homozygous intragenic GNPTAB gene deletion (c.3435-386_3602 + 343del897) encompassing exon 19, identified in a ML II α/β patient. Long-range PCR and sequencing methodologies were used to refine the characterization of this rearrangement, leading to the identification of a 21 bp repetitive motif in introns 18 and 19. Further analysis revealed that both the 5' and 3' breakpoints were located within highly homologous Alu elements (Alu-Sz in intron 18 and Alu-Sq2, in intron 19), suggesting that this deletion has probably resulted from Alu-Alu unequal homologous recombination. RT-PCR methods were used to further evaluate the consequences of the alteration for the processing of the mutant pre mRNA GNPTAB, revealing the production of three abnormal transcripts: one without exon 19 (p.Lys1146_Trp1201del); another with an additional loss of exon 20 (p.Arg1145Serfs*2), and a third in which exon 19 was substituted by a pseudoexon inclusion consisting of a 62 bp fragment from intron 18 (p.Arg1145Serfs*16). Interestingly, this 62 bp fragment corresponds to the Alu-Sz element integrated in intron 18.This represents the first description of a large deletion identified in the GNPTAB gene and contributes to enrich the knowledge on the molecular mechanisms underlying causative mutations in ML II. | por |
| dc.description.sponsorship | This work was supported by FCT - project PIC/IC/83252/2007 (http://alfa.fct.mctes.pt/). Coutinho MF and Quental S received grants from the FCT (SFRH/BD/48103/2008; SFRH/BPD/64025/2009). | por |
| dc.identifier.citation | JIMD Rep. 2012;4:117-24. doi: 10.1007/8904_2011_83. Epub 2011 Oct 20 | por |
| dc.identifier.other | doi: 10.1007/8904_2011_83 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/1524 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | SSIEM/Springer-Verlag | por |
| dc.relation.publisherversion | http://link.springer.com/chapter/10.1007%2F8904_2011_83# | por |
| dc.subject | Doenças Genéticas | por |
| dc.subject | Mucolipidosis II | por |
| dc.title | Alu-Alu Recombination Underlying the First Large Genomic Deletion in GlcNAc-Phosphotransferase Alpha/Beta (GNPTAB) Gene in a MLII Alpha/Beta Patient | por |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 124 | por |
| oaire.citation.startPage | 117 | por |
| oaire.citation.title | JIMD Reports | por |
| oaire.citation.volume | 4 | por |
| rcaap.rights | openAccess | por |
| rcaap.type | article | por |