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Please use this identifier to cite or link to this item: http://hdl.handle.net/10400.18/804

Título: Evidences of large deletions in patients with the Lysosomal Storage Diseases Mucolipidosis type II and III: experimental approaches for picking up both homozygous and heterozygous cases
Autor: Coutinho, Maria Francisca
Encarnação, Marisa
Carvalho, Filipa
Lacerda, Lúcia
Willbrand, Flemming
Ribeiro, Helena
Prata, Maria João
Alves, Sandra
Palavras-chave: Doenças Genéticas
Issue Date: Nov-2010
Editora: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Resumo: Backgroung/Objectives: Mucolipidosis II and III are rare genetic diseases in which the activity of the uridine diphosphate (UDP)-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) is reduced or absent. GlcNAc-phosphotransferase is a multimeric enzyme encoded by two genes: GNPTAB and GNPTG. Although a wide spectrum of mutations in GNPTAB has recently been reported to cause ML II and III alpha/beta, large deletions have not yet been reported. Furthermore, some previously reported patients present only one heterozygous mutation while the second one is still missing. Here we present evidence that some of these cases may be due to the difficulty to detect large heterozygous deletions through direct sequencing. Methods: We developed a semiquantitative approach by multiplex PCR and capillary electrophoresis, co-amplifying two fragments in each PCR reaction: one corresponding to GNPTAB exons and the other to an internal control fragment. Results: After applying this technique to perform a genomic screen in two Portuguese patients in whom a heterozygous missense was identified while the second mutation was missing, we found that in both patients the last exons (20 and 21) of the GNPTAB gene were missing in one of the alleles. We also found and characterize a gross homozygous deletion involving exon 19 in one Danish patient. Conclusion: Here we present a molecular approach that turned possible to identify for the first time large deletions in the GNPTAB, underlying mucolipidoses in patients who were both homozygous and heterozygous for such alterations. Our semiquantitative PCR based method is a valuable tool that allows the screening of large deletions. Consequently, we propose that cases with only one heterozygous mutation detected through direct sequencing methods, should be further screened for the possible presence of a large heterozygous deletion.
Arbitragem científica: yes
URI: http://hdl.handle.net/10400.18/804
Appears in Collections:DGH - Posters/abstracts em congressos internacionais

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