Coutinho, Maria FranciscaEncarnação, MarisaLaranjeira, FranciscoLacerda, LúciaPrata, Maria JoãoAlves, Sandra2017-02-202017-02-202016-10-21J Pediatr Endocrinol Metab. 2016 Oct 1;29(10):1225-1228. doi: 10.1515/jpem-2016-01730334-018Xhttp://hdl.handle.net/10400.18/4286While being well known that the diagnosis of many genetic disorders relies on a combination of clinical suspicion and confirmatory genetic testing, not rarely, however, genetic testing needs much perseverance and cunning strategies to identify the causative mutation(s). Here we present a case of a thorny molecular diagnosis of mucolipidosis type III alpha/beta, which is an autosomal recessive lysosomal storage disorder, caused by a defect in the GNPTAB gene that codes for the α/β-subunits of the GlcNAc-1-phosphotransferase. We used both cDNA and gDNA analyses to characterize a mucolipidosis type III alpha/beta patient whose clinical diagnosis was already confirmed biochemically. In a first stage only one causal mutation was identified in heterozygosity, the already described missense mutation c.1196C>T(p.S399F), both at cDNA and gDNA levels. Only after conducting inhibition of nonsense-mediated mRNA decay (NMD) assays and after the utilization of another pair of primers the second mutation, the c.3503_3504delTC deletion, was identified. Our findings illustrate that allelic dropout due to the presence of polymorphisms and/or of mutations that trigger the NMD pathway can cause difficulties in current molecular diagnosis tests.engAllelic DropoutGenotype-phenotype CorrelationGlcNAc-1-phosphotransferaseGNPTABML III alpha/betaMolecular Genetic TestingNonsense Mediated mRNA DecayPolymorphismDoenças Genéticasjournal article10.1515/jpem-2016-0173