With the invention of RNA sequencing over a decade ago, diagnosis and identification of the gene-related diseases entered a new phase that enabled more accurate analysis of the diseases that are difficult to approach and analyze. RNA sequencing has availed in-depth study of transcriptomes in different species and provided better understanding of rare diseases and taxonomical classifications of various eukaryotic organisms. Development of single-cell, short-read, long-read and direct RNA sequencing using both blood and biopsy specimens of the organism together with recent advancement in computational analysis programs has made the medical professional’s ability in identifying the origin and cause of genetic disorders indispensable. Altogether, such advantages have evolved the treatment design since RNA sequencing can detect the resistant genes against the existing therapies and help medical professions to take a further step in improving methods of treatments towards higher effectiveness and less side effects. Therefore, it is of essence to all researchers and scientists to have deeper insight in all available methods of RNA sequencing while taking a step-in therapy design.

Genome editing techniques are considered to be one of the most challenging yet efficient tools for assisting therapeutic approaches. Several studies have focused on the development of novel methods to improve the efficiency of gene editing, as well as minimise their off-target effects. clustered regularly interspaced short palindromic repeats (cRISPR)-associated protein (cas9) is a tool that has revolutionised genome editing technologies. New applications of cRISPR/cas9 in a broad range of diseases have demonstrated its efficiency and have been used in ex vivo models of somatic and pluripotent stem cells, as well as in in vivo animal models, and may eventually be used to correct defective genes. The focus of the present review was the recent applications of cRISPR/cas9 and its contribution to the treatment of challenging human diseases, such as various types of cancer, neurodegenerative diseases and a broad spectrum of other disorders. cRISPR technology is a novel method for disease treatment, enhancing the effectiveness of drugs and improving the development of personalised medicine.

Purpose. Early infantile epileptic encephalopathy (EIEE) 57 belongs to a group of encephalopathies with early-onset and characterised by severe electroencephalogram abnormalities, seizures, developmental delay and intellectual disability. Method. We carried out Whole Exome analysis using Next Generation Sequencing (NGS) and bioinformatic analysis performed to find mutation associated with the patient phenotypes. The effect of the mutation on protein structure analysed by PolyPhen2 and Swissmodel ExPASy. Results. In this study, we evaluated two unrelated Turkish males diagnosed with EIEE type 57 to investigate the genetic cause of this disease. Whole exome sequencing revealed mutations in KCN2 gene, which is a member of Potassium channels (KCN) gene family associated with epileptic encephalopathies. Two mutations, c.545A>T (p.Asn182Ile and c.2638C>A (p.Leu880Met) were reported here as a novel mutation. Conclusions. Our findings implicate the genotype-phenotype correlation of these mutations. Furthermore, the computational analysis showed their effect on protein binding site and function suggesting their role in the development of early infantile epileptic encephalopathy 57.

The condition 3-methylglutaconic aciduria (3-MGA) with deafness, encephalopathy and Leigh-like (MEGDEL) syndrome, also known as 3-MGA IV, is one of a group of five rare metabolic disorders characterized by mitochondrial dysfunction, resulting in a series of phenotypic abnormalities. It is a rare, recessive inherited disorder with a limited number of cases reported worldwide; hence, it is important to study each case to understand its genetic complexity. An impaired activity of serine active site-containing protein 1 (SERAC1), caused by mutations, leads to defects in phosphatidylglycerol remodelling, which is important for mitochondrial function and intracellular cholesterol trafficking. In the present study, the patients (two male siblings of consanguineous Turkish parents) were analysed, whose multisystem dysfunctions, including an elevated 3-MGA concentration in early age, hearing loss and Leigh-like syndrome as determined by MRI, were consistent with MEGDEL syndrome. A novel mutation in the SERAC1 gene, in the upstream lipase domain, c.1015G>C (p.Gly339Arg) mutation located on exon 10 of the SERAC1, was identified and predicted to cause protein dysfunction. Furthermore, the results pointed towards a possible association between this mutation and the severity of MEGDEL syndrome.

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X-lined intellectual disability (XLID), formerly known as X-lined mental retardation, is defined as genetically heterogeneous disorders with remarkable cognitive impairment and abnormal adaptive behaviour skills. This study demonstrates the Disc-large homolog 3 (DLG3) gene impairment in 2 different unrelated male probands. The results detected two missense mutations in the DLG3 gene, c.2267 G > A (p.Arg756Gln) and c.2359G > A p. (Gly787Ser) using by NGS. Both mutations were run in the PolyPhen2 program for mutation sensitivity check and showed to have 0.709 and 1, respectively. The familial transmission pattern of MR detected both mothers to be heterozygote. The mutations were shown to have caused non-syndromic XLMR (NS-XLMR) as both males did not show any abnormal facial or physiological features. Based on the IQ measurement, proband 1 and 2’ IQs were measured 40 and 33, and they were diagnosed with moderate and severe XLMR, respectively. Both affected males showed significant deterioration in neural development and behaviour abilities, which indicates the significant impact of the mutation on neurotransmitters and maintenance of NMDA receptors in neural functions. However, further molecular and functional studies are necessary to provide more conclusive evidence of the detailed abnormalities caused by the reported mutations.