Publication
Alu-Alu recombination underlying the first large genomic deletion in GlcNAc-phosphotransferase α/β (GNPTAB) gene in a MLII α/β 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 | Flemming, W | |
| dc.contributor.author | Lund, AM | |
| dc.contributor.author | Johansen, KB | |
| dc.contributor.author | Prata, Maria João | |
| dc.contributor.author | Alves, Sandra | |
| dc.date.accessioned | 2012-02-29T15:37:41Z | |
| dc.date.available | 2012-02-29T15:37:41Z | |
| dc.date.issued | 2011-10-20 | |
| dc.description.abstract | Mucolipidosis type II alpha/beta is a severe, autosomal recessive lysosomal storage disorder, caused by a defect in the GNPTAB gene that codes for the alpha/beta subunits of the GlcNAc-phosphotransferase. To date, over 100 different mutations have been identified in MLII alpha/beta 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 alpha/beta patient. Long range PCR and sequencing methodologies were used to refine the characterization of this rearrangement, leading to the identification of a 21bp 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.identifier.citation | JIMD Reports 2011; 4:117-124. Epub 2011 Out 20 | por |
| dc.identifier.issn | 2192-8304 | |
| dc.identifier.other | doi:10.1007/8904_2011_83 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/704 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Springer Verlag | por |
| dc.relation.publisherversion | http://www.springerlink.com/content/k042607857q83658/ | por |
| dc.subject | Doenças Genéticas | por |
| dc.title | Alu-Alu recombination underlying the first large genomic deletion in GlcNAc-phosphotransferase α/β (GNPTAB) gene in a MLII α/β patient | por |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 124 | por |
| oaire.citation.startPage | 117 | por |
| oaire.citation.title | Journal of Inherited Metabolic Disease | por |
| rcaap.rights | restrictedAccess | por |
| rcaap.type | article | por |