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Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III - identification of eight novel mutations

2009-07Journal article Restricted access
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dc.contributor.authorEncarnação, Marisa
dc.contributor.authorLacerda, Lúcia
dc.contributor.authorCosta, Roberto
dc.contributor.authorPrata, Maria João
dc.contributor.authorCoutinho, Maria Francisca
dc.contributor.authorRibeiro, Helena
dc.contributor.authorLopes, Lurdes
dc.contributor.authorPineda, M.
dc.contributor.authorIgnatius, J.
dc.contributor.authorGalvez, H.
dc.contributor.authorMustonen, A.
dc.contributor.authorVieira, P.
dc.contributor.authorLima, Margarida Reis
dc.contributor.authorAlves, Sandra
dc.date.accessioned2012-02-28T12:37:28Z
dc.date.available2012-02-28T12:37:28Z
dc.date.issued2009-07
dc.description.abstractMucolipidosis II (ML II) and mucolipidosis III (ML III) are diseases in which the activity of the uridine diphosphate (UDP)-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) is absent or reduced, respectively. In the absence of mannose phosphorylation, trafficking of lysosomal hydrolases to the lysosome is impaired. In these diseases, mistargeted lysosomal hydrolases are secreted into the blood, resulting in lysosomal deficiency of many hydrolases and a storage-disease phenotype. GlcNAc-phosphotransferase is a multimeric transmembrane enzyme composed of three subunits (alpha, beta and gamma) encoded by two genes -GNPTAB and GNPTG. Defects in GNPTAB result in ML II and III whereas mutations in GNPTG were only found in ML III patients. We have performed a molecular analysis of the GNPTAB and GNPTG genes in 13 mucolipidosis II and III patients (10 Portuguese, one Finnish, one Spanish of Arab origin and one Indian). Mutations were identified by the study of both cDNA and gDNA. The GNPTAB and GNPTG mRNA expressions were determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The study led to the identification of 11 different mutations. Eight of these mutations are novel, six in the GNPTAB gene [c.121delG (V41FfsX42), c.440delC (A147AfsX5), c.2249_50insA (N750KfsX8), c.242G>T (W81L), c.1208T>C (I403T) and c.1999G>T (p.E667X)] and two in the GNPTG gene [c.610-1G>T and c.639delT (F213LfsX7)]. With regard to the mRNA expression studies, the values obtained by qRT-PCR indicate the possible existence of feedback regulation mechanisms between alpha/beta and the gamma subunits.por
dc.identifier.citationClin Genet. 2009 Jul;76(1):76-84por
dc.identifier.issn0009-9163
dc.identifier.otherdoi:10.1111/j.1399-0004.2009.01185.x
dc.identifier.urihttp://hdl.handle.net/10400.18/681
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherJohn Wiley and Sonspor
dc.relation.publisherversionhttp://onlinelibrary.wiley.com/doi/10.1111/j.1399-0004.2009.01185.x/abstractpor
dc.subjectDoenças Genéticaspor
dc.subjectMucolipidosis IIpor
dc.subjectMucolipidosis IIIpor
dc.titleMolecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III - identification of eight novel mutationspor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleClinical Geneticspor
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor

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