The Subject

Otukesh et al. (2009) show that the association between NPHS1 and NPHS2 genes and nephrotic syndrome has been the subject of numerous genetic research. However, the role of the other specific genetical mutations in the NPHS1 gene in the pathogenicity and clinical presentation of the disease had not been established (Lipska et al. 2013). This research gap was adequately utilised by Tory et al. (2014) who not only establishes the role of the mutations but also explains their role in specific clinical presentation of the disease.

Methodology

Tory et al. (2014) use retrospective cohort study methodology for the screening of unaffected obligate mutation carriers for p.Arg229Gln. The cohort of the study was parents of children with non-p.Arg229Gln NPHS2 mutations on both the alleles. The researchers then do a retrospective identification of the risk factor, the presence of p.Arg229Gln. Therefore, the screening of the mutations by ClaI digestion was used to establish the risk factor for the inheritance of the disease. The use of a retrospective cohort study design was very appropriate for testing the first hypotheses of the study. This is because cohort studies designs allows for the establishment of the association between two or more variables; the exposure to the risk factor and one or more outcomes (Euser et al. 2009).

The use of a cohort study is also important in establishing the effects of rare exposures (Levin 2006). Conventionally, it is not expected that there should be any carrier for an autosomal recessive disorder as per the Mendel’s law (Kugler 2002). The pathogenicity of the mutations are multiple, and therefore adoption of cohort study design methodology was suitable.

Tory et al. (2014) also used a systematic literature review to analyse the frequency of alleles in NPHS2 mutations. Perhaps this was suitable for obtaining numerous research data from the database so as to provide an extensive body of evidence. However, an analysis of known cohorts could have been better for this study in order to accurately determine the frequency of the alleles in the mutation. According to Garg et al. (2008), systematic reviews are suitable when the research focuses on the appraisal and synthesis of empirical evidence. In the background, the researchers explained that there was no study that reported the mutation-dependance as a factor in the inheritance of steroid-resistant nephrotic syndrome. Therefore, it is wrong for the study to adopt the systematic review of using studies that did not specifically study the subject of interest. The use of cohorts from the different studies in PubMed for genetic analysis is however commendable. This is because the cohorts reduces selection and recall bias during the retrospective cohort study.

Finally, the study also uses an experimental study approach to generating podocin-coding plasmids, to culture podocyte cell lines and urine sediments, to analyse the subcellular localization of podocin and to perform molecular modeling of podocin dimerization. This part of the study required a critical analysis of the protein encoded by the mutant gene. Therefore, the use of an experimental study design to analyse the molecular structure of the protein was suitable. As argued by Knight (2010), experimental designs enable the researchers to have absolute control over variables. The design is also appropriate for an easy and accurate determination of the cause and effect relationship (Knight 2010). In this research, there was need to eliminate the irrelevant variables and at the same time determine the structure of the mutated protein in order to associate its structure to the disorder. Therefore, Tory et al. (2014) were justified in using the design for the analysis of the protein.