Functional analysis of novel splicing and missense mutations identified in the ASS1 gene in classical citrullinemia patients
Clinica chimica acta; international journal of clinical chemistry, 2015
Classical citrullinemia (CTLN1) is an inborn error of the urea cycle caused by reduced/abolished ... more Classical citrullinemia (CTLN1) is an inborn error of the urea cycle caused by reduced/abolished activity of argininosuccinate synthetase due to mutations in the ASS1 gene. To determine the pathogenicity of novel variants detected in patients is often a huge challenge in molecular diagnosis. The purpose of our study was to characterize novel ASS1 gene mutations identified in CTLN1 patients. Exon trapping assay with pSPL3 was used to confirm splice aberrations while bioinformatics structural analysis predicted the possible effects of missense mutations. Novel donor site (c.174+1G>A) and missense (p.V141G) mutations were detected in a patient exhibiting a biochemical phenotype only. The splice mutation provoked exon skipping hence the truncated product. The mutation p.V141G, is predicted to disturb a hydrophobic pocket in the ATP binding domain in the ASS. Both mutations are predicted to lower binding of ATP. The second patient presented with early onset neonatal citrullinemia mark...
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Papers by joseph kimani