Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/1524
Título: Alu-Alu Recombination Underlying the First Large Genomic Deletion in GlcNAc-Phosphotransferase Alpha/Beta (GNPTAB) Gene in a MLII Alpha/Beta Patient
Autor: Coutinho, Maria Francisca
da Silva Santos, Liliana
Lacerda, Lúcia
Quental, Sofia
Wibrand, F.
Lund, A.M.
Johansen, K.B.
Prata, Maria João
Alves, Sandra
Palavras-chave: Doenças Genéticas
Mucolipidosis II
Data: Abr-2012
Editora: SSIEM/Springer-Verlag
Citação: JIMD Rep. 2012;4:117-24. doi: 10.1007/8904_2011_83. Epub 2011 Oct 20
Resumo: 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.
Peer review: yes
URI: http://hdl.handle.net/10400.18/1524
Versão do Editor: http://link.springer.com/chapter/10.1007%2F8904_2011_83#
Aparece nas colecções:DGH - Artigos em revistas internacionais

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