A patient with PLACK syndrome with a novel splicing mutation in CAST: the evidence for a loss-of-function mechanism through mis-splicing.

PLACK syndrome is a relatively recently defined generalized peeling skin syndrome that has been reported with major skin manifestations and sometimes atypical features. We report the case of a 5-year-old boy with PLACK manifestations. Whole exome sequencing and subsequent Sanger sequencing identified a putative splice variant c.1209+2T>G in CAST (NM_001042440.5). Moreover, mRNA sequencing confirmed the abnormal alternative splicing of the CAST gene, leading to the addition of one nucleotide to the correct open-reading frame at the mRNA level. Segregation and expression analysis revealed that this loss-of-function via mRNA nonsense-mediated decay could be the causative pathogenic mechanism responsible for this patient's phenotype. This study extends our understanding of the various phenotypic and genotypic features of PLACK syndrome.

CRISPR-Based Fluorescent Reporter (CBFR) Assay for Sensitive, Specific, Inexpensive, and Visual Detection of a Specific EGFR Exon 19 Deletion in NSCLC.

Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. Mutations in the EGFR gene, including deletions in exon 19 and the mutation L858R, induce responsiveness of non-small cell lung cancer (NSCLC) to a group of drugs known as tyrosine kinase inhibitors. Here, we report the development of the CRISPR-based fluorescent reporter (CBFR) assay including a two-step strategy combining PCR amplification and Cas12a-driven cleavage to detect the delE746_A750 subtype of EGFR exon 19 deletions. Sensitivity and specificity of the CBFR assay were analyzed with different concentrations of fluorescence reporter and different amounts of PCR product. The results demonstrated that increasing the fluorescent reporter to 4 µM and the PCR product to 5 µl enhanced sensitivity. The CBFR assay could detect EGFR exon 19 deletion even with a frequency of 1% in samples. In clinical NSCLC samples, optimized CBFR assay enabled visual detection of the delE746_A750 subtype in less than 1 h. The CBFR assay provides a sensitive, specific, and simple strategy designed based on a straightforward and inexpensive process. We suggest that the CBFR assay could serve as a diagnostic approach to detect mutations, deletions, and pathogens in underequipped laboratories and promote personalized therapeutic approaches.

Data mining of bulk and single-cell RNA sequencing introduces OBI1-AS1 as an astrocyte marker with possible role in glioma recurrence and progression.

Long non-coding RNAs (LncRNAs) are widely known for their various functions in cancer from tumor initiation to tumor progression and metastasis. Gliomas are the most prevalent primary forms of brain tumor, classified into grades I to IV according to their malignant histological features with grade IV, also known as glioblastoma multiforme (GBM), displaying the highest level of malignancy. Thus, the search for differentially expressed LncRNAs in GBM versus low-grade glioma to uncover new insights into the molecular mechanisms of glioma progression have intensified. Bulk RNA sequencing pinpointed decreased expression of OBI1-AS1 in GBM compared to low-grade glioma samples. Subsequent single nuclei RNA sequencing revealed OBI1-AS1 to be a super-exclusive astrocyte marker with AUC = 0.99 and the potential to fully differentiate astrocytes from other brain cell types. Additional supplementary bioinformatics analysis exhibited OBI1-AS1 role in synaptic signal transduction and glutamatergic signaling. In addition, ChIP-Seq data were analyzed to explore transcription factors that can regulate OBI1-AS1 expression in neural cells. Results of Hi-C, methylation and ChIP-Seq analysis strongly suggest methylation of the CTCF binding site serving a central role in regulation of OBI1-AS1 expression via managing chromatin interactions. Our study indicated that lncRNAs, like OBI1-AS1, could be extremely precise in identifying the astrocyte cluster in the single-cell transcriptome and demonstrating superiority to well-established astrocyte markers such as GFAP, S100B, ALDH1L1, and AQP4.

Molecular and clinical characterization of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) in Iranian non-Jewish patients: report of two novel AIRE gene pathogenic variants.

OBJECTIVE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) is a rare autosomal recessive systemic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Incidence of this genetic disorder is estimated at 1/90,000-200,000 worldwide and 1/6500-9000 in genetically isolated populations such as Iran. Here, we investigated AIRE gene mutations in eight independent Iranian non-Jewish families. METHODS: We sequenced the coding regions of the AIRE gene and documented mutations which were further confirmed in respective parents. RESULTS: In total, 11 cases from 8 independent families were recruited. Mucosal candidiasis, Addison's disease and hypoparathyroidism were the most common clinical manifestations in these patients. One novel homozygous splice acceptor mutation (c.308-1G>C), and one novel heterozygous stop-gain mutation (c.1496delC) combined with a known heterozygous c.232T>C missense mutation were found. Moreover, we observed previously described splice donor (c.1095+2T>A), frameshift (c.967-979del), stop-gain (c.415C>T), and missense (c.62C>T) mutations among the patients. All results were co-segregated in parents. CONCLUSION: Here, we reported two novel mutations in the AIRE gene leading to APECED. Our data could provide insight into the phenotypic and genotypic spectrum of APECED in the non-Jewish Iranian population. These findings, in addition to future functional assays, can elucidate disease-causing mechanisms related to the AIRE gene and assist in genetic counseling and diagnosis.

Differential Expression of Hypoxia-Related Genes in Primary Brain Tumors and Correlation with Clinicopathologic Data.

OBJECTIVE: Meningiomas and gliomas are common benign and malignant primary brain tumors, respectively. One of the most prominent features of aggressive malignancies contributing to their progression is their ability to cope with hypoxia. Therefore, glioma tumors are expected to better cope with adverse hypoxic conditions and, consequently, display significantly different expression levels of hypoxia-adaptive genes. METHODS: Thirty-three glioma (17 glioblastoma multiforme [GBM], 16 low-grade glioma [LGG]) and 32 meningioma samples were investigated for expression of hypoxia adaptation- related genes by real-time polymerase chain reaction. The same investigation was carried out for GBM, the most malignant form of glioma, versus LGG. The findings were further checked by bioinformatics analysis of expression levels using RNA-seq data. Additional investigations conducted include receiver operating characteristic curve analysis to assess the power for each gene in differential diagnosis of glioma from meningioma. RESULTS: A greater level of hypoxia-inducible factor (HIF) 1α expression in glioma samples compared with meningioma and greater expression levels of Yes-associated protein (YAP) 1 and G-protein-coupled receptor class C group 5 member A (GPRC5A) in meningioma were observed, with P values 0.0005, <0.0001, and <0.0001 for GPRC5A, HIF1α, and YAP1, respectively. Comparison of GBM with LGG also revealed GPRC5A to have significantly greater expression in GBM with P = 0.0381. The calculated area under the curve was 0.7536, 0.8438, and 0.8272 for GPRC5A, HIF1α, and YAP1, respectively, which represented acceptable power for these genes in differential diagnosis of glioma tumor types from meningioma and tumor subtypes GBM from LGG under study. CONCLUSIONS: These results imply that these genes can possibly be implicated in brain tumor hypoxia-adaptation response with tumor-specific roles and patterns of expression.

Decreased Sox2 Messenger RNA Expression in Basal Cell Carcinoma.

BACKGROUND: Sox2, zeb1, and p21 have been implicated in aggressive behavior of squamous cell carcinoma (SCC) and melanoma. However, their expression level in basal cell carcinoma (BCC) has not been elucidated. We hypothesized BCC, contrary to SCC, and melanoma, could be a suitable model to study mechanisms which attenuate tumor metastasis. The aim of this study was to examine the messenger RNA (mRNA) expression levels of sox2, zeb1, and p21 in BCC. MATERIALS AND METHODS: Twenty-seven nonmetastatic BCC and twelve normal skin samples were evaluated using real-time reverse transcriptase polymerase chain reaction. RESULTS: The stemness marker sox2 demonstrated marked down-regulation, but zeb1 and p21 showed no significant change. CONCLUSIONS: Here, we report a negative association between sox2 mRNA expression level and nonmetastatic BCC, thus, providing a likely explanation for the fact that normal skin is more reliant on sox2 than BCC. BCC may be using decreased sox2 mRNA to remain incognito from metastatic potential.

Catechol-O-methyltransferase gene expression in stress-induced and non-stress induced schizophrenia.

INTRODUCTION: As schizophrenia is a complex mental disorder and the outcome of gene-gene-environmental interactions, there are different possible pathophysiological mechanisms in different schizophrenia subtypes corresponding to various risk factors. This study was aimed at examining the impact of one of the most likely interactions, that is, 'dopamine and stress', in schizophrenia pathogenesis. METHODS: Here, we investigated the interaction between 'war-related psychological trauma' without brain trauma and catechol-O-methyltransferase gene. Using real-time PCR analysis we measured catechol-O-methyltransferase gene expression level in the blood cells of 66 male subjects in four groups, namely veteran schizophrenia patients as 'stress-exposed schizophrenia' (S-schizophrenia), their healthy brothers as 'their genetically closest relatives' (S-siblings), schizophrenia patients without any history of significant stress as 'non-stress-exposed schizophrenia' (NoS-schizophrenia), and the control group. The results were analyzed by Relative Expression Software Tool 2009 software. RESULTS: The catechol-O-methyltransferase gene expression was not significantly different between the S-schizophrenia and NoS-schizophrenia groups. However, compared to the control group, the catechol-O-methyltransferase expression was significantly decreased in three groups of S-schizophrenia, their healthy siblings, and NoS-schizophrenia patients. CONCLUSION: This data supports that reduced blood catechol-O-methyltransferase expression, which may be associated with higher dopamine level, is involved both in stress-induced and non-stress-induced schizophrenia.

Molecular investigation of mutations in androgen receptor and 5-alpha-reductase-2 genes in 46,XY Disorders of Sex Development with normal testicular development.

In this study, we aimed to determine androgen receptor (AR) and SRD5A2 gene mutations in 45 patients characterised by 46,XY Disorders of Sex Differentiation (DSD) signs with normal testicular development referred to the Children's Medical Center from February 2015 to September 2017. Karyotype and sex hormone analyses were performed. Cytogenetic investigation showed that seven patients were 46,XX DSD, six patients were chromosomal DSD and 32 patients were 46,XY DSD. Eight exons of the AR gene and five exons of the SRD5A2 gene were amplified. Two cases were affected with androgen insensitivity syndrome (AIS) (missense mutation on exon 7, position c.3637 G>A: p.R841H and position c.3610 G>A: p.R832Q), one case was affected with 5-alpha-reductase deficiency type 2 (missense mutation at c.578A>G: p.N193S on exon 4), and 22 cases (88%) did not demonstrate AIS or 5α-RD2 gene abnormality. Due to the great impact of these disorders on human lifestyle, evaluation of genes involved can improve genetic counselling and therapeutic management. We focused on the AR and SRD5A2 genes in patients with 46,XY DSDs with normal testicular development referred to the Children's Medical Center from all over the country to eventually culminate in a reliable prenatal diagnosis protocol at this major referral centre giving service to a great number of families with consanguineous marriages.

Detection of CCND1 , C-MYC , and FGFR1 amplification using modified SYBR Green qPCR and FISH in breast cancer

Background/aim: The aims of this study were to detect CCND1 , C-MYC , and FGFR1 amplification using qPCR, confirmation with FISH, and to further assess their clinicopathological relevance. Materials and methods: Thirty-five breast tumor samples were analyzed for amplification of the selected genes using modified SYBR Green qPCR. The accuracy of the qPCR was assessed by FISH as a gold-standard method. Results: CCND1 , C-MYC , and FGFR1 amplifications were observed in 34.28%, 28.57%, and 17.14% of the 35 samples, respectively. qPCR results were significantly confirmed by FISH and qPCR and FISH showed excellent correlation (P = 0.000). CCND1 amplification with tumor stage (P = 0.044), positive metastatic status (P = 0.042), positive family history (P = 0.042), and C-MYC status (P = 0.005); C-MYC amplification with tumor size (P = 0.021), tumor grade (P = 0.018), tumor stage (P = 0.032), and FGFR1 status (P < 0.000); and FGFR1 amplification with tumor size (P = 0.041) and positive ER status (P = 0.042) were statistically associated. Conclusion: Our findings revealed that the applied qPCR approach could precisely quantify the relative gene copy number. More studies with a larger sample size are suggested to confirm the clinicopathological value of CCND1 , C-MYC , and FGFR1 amplification.

Healthy Adult LDL-C Bears Reverse Association with Serum IL-17A Levels.

BACKGROUND: Hypercholesterolemia is a modifiable risk factor in atherosclerosis with a complex association with inflammation. OBJECTIVE: In the present study, the association between low-density lipoprotein cholesterol (LDL-C) and interleukin 17A (IL-17A), as an inflammatory cytokine, was investigated. In addition to IL-17A, serum levels of interleukin 23 (IL-23) and transforming growth factor ß (TGF-ß), as effective cytokines in T helper 17 cell (Th17) development, were also determined. METHOD: Cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA) in healthy subjects with LDL-C<130 versus LDL-C=>130 mg/dL. RESULTS: Although IL-17A is an inflammatory cytokine and a positive association between its levels and LDL-C is expected, the data obtained in this study provide support for a reverse association (p<0.05). CONCLUSION: Inflammation plays a major role in atherosclerosis development; however, various inflammatory components involved in atherosclerosis assert their own unique association with hypercholesterolemia.

Specific immune responses induced by multi-epitope DNA derived from Mycobacterium tuberculosis DosR antigens.

One third of the world population are latently infected with Mycobacterium tuberculosis and are at the risk of reactivation of tuberculosis (TB). The most effective strategy for control of TB worldwide is the development of a vaccine that inhibits progression of latent TB to active infection. In this study, two optimized constructs consisting of multi-epitopes DNA derived from three latency antigens Rv2029c, Rv2031c, and Rv2627c fused with or without light chain 3 (LC3) are synthetized. The immunogenicity effectiveness of two DNA constructs was evaluated in the mouse model. LC3-fused multi-epitope DNA construct induced strong specific Th1 immune responses with high increase in IFN-γ+ CD4+ and IL-2+ CD4+ T cell populations (both with p < 0.0001) and IFN-γ+ IL-2+ CD4+ T cell population (p < 0.0001) compared with empty vector, BCG, and multi-epitope DNA construct groups. The LC3-fused construct induced IFN-γ+ CD8+ T cell population (p < 0.0001) compared with empty vector and BCG groups but could not induce the T cell population compared with construct without LC3. Importantly, LC3-fused DNA construct did not induce epitope-specific IL-4 and IL-10 from CD4+ and CD8+ T cell populations. The results indicated that LC3-fused multi-epitope DNA construct has a potential to be investigated for future development of a new TB vaccine.

Modified methylated DNA immunoprecipitation protocol for noninvasive prenatal diagnosis of Down syndrome.

AIM: Methylated DNA immunoprecipitation real-time quantitative polymerase chain reaction (MeDIP-real-time qPCR) has been introduced as noninvasive prenatal test that has shown absolute detection rate in the screening of Down syndrome. Herein, we aimed to propose a novel modification of MeDIP-qPCR and assess its potential to alleviate the overall cost of the test, being used in very early weeks of pregnancy, and develop it to a noninvasive prenatal diagnosis biosensor in future researches. METHODS: Cell-free fetal DNA (cffDNA) isolated from 60 pregnant women, including 29 normal and 31 trisomy 21 pregnancies, were analyzed using proposed MeDIP protocol. Enriched methylated DNA sequences were amplified through real-time qPCR using eight fetal-specific primer pairs. The status of samples was determined through the calculation of D-value with the cutoff point of zero. RESULTS: The sensitivity and specificity of the MeDIP protocols using nanoparticles were 100% and 100%, respectively. CONCLUSION: Remarkable decrease in the price of MeDIP test per each patient would be a reasonable factor to confirm it on larger sample size. Moreover, the high detection rate of screening and the availability of the required instruments around the world make satisfactory reasons to be tested in earlier weeks of pregnancy, thanks to the high sensitivity of gold shell nanoparticles.

Association of transcription factor 4 (TCF4) gene mRNA level with schizophrenia, its psychopathology, intelligence and cognitive impairments.

Schizophrenia (SCZ), is considered as one of the most debilitating mental disorders around the world. Symptom-based clinical interview and numerous tests have been used to evaluate the diagnosis and also cognitive disturbances in patients with SCZ. All these tests measure phenotype-based functions. Thus, it seems accurate diagnosis of such complex disorders must rely on more valid and reliable factors. In this study, we evaluated the association of transcription factor 4 (TCF4) gene mRNA level in peripheral blood with SCZ, and also its psychopathology, cognitive and intellectual impairments. In this study, using real-time PCR, we compared TCF4 mRNA level between the case (70 unmedicated schizophrenia patients) and healthy control (n = 72) groups. In addition, all subjects underwent Psychopathology (PANSS) and cognitive and intelligence (WAIS, WMS, Stroop, WCST) assessments, and scores were compared between the two groups. Also, to determine the effect of TCF4 expression on psychopathology, cognitive and intellectual functions, the correlation between expression level and test scores was measured. The correlation between gene expression and age of onset and duration of the disorder was evaluated as well. Our results showed that the TCF4 mRNA level, psychopathology, cognitive and intellectual functions were significantly different in all, male, and female patients compared to healthy participants. Additionally, it was found that TCF4 level is positively correlated with scores of WAIS and WMS and is negatively correlated with Stroop and WCST errors and PANSS score. Our results showed that the mRNA level of TCF4 may be associated with SCZ, its psychopathology, IQ and cognitive impairments in an Iranian group of patients with SCZ. These results may help to better understanding the TCF4 role in the psychopathogenesis of SCZ and also may shed some light on the ongoing works conducted on peripheral biomarker-based diagnosis of complicated mental disorders.

Very early onset inflammatory bowel disease: Investigation of the IL-10 signaling pathway in Iranian children.

BACKGROUND & AIM: Comparing to adult inflammatory bowel disease (IBD), those with early onset manifestations have different features in terms of the underlying molecular pathology, the course of disease and the response to therapy. We investigated the IL-10 signaling pathway previously reported as an important cause of infantile (Very Early Onset) IBD to find any possible variants. METHOD: With the next generation sequencing technique we screened IL-10, IL-10RA and IL10RB genes of 15 children affected by very early onset-GI (gastrointestinal) disorders. Additionally, we analyzed them based on Thermo Fisher immune deficiency panel for genes either having a known role in IBD pathogenesis or cause the disorders with overlapping manifestations. We performed multiple functional analyses only for the cases showing variants in IL-10- related genes. RESULT: In 3 out of 15 patients we identified variants including a homozygous and heterozygote mutations in IL-10RA and a novel homozygous mutation in IL-12RB1. Our functional studies reveal that in contrast to the IL-10RA heterozygote mutation that does not have deleterious effects, the homozygous mutation abrogates the IL-10 signaling pathway. CONCLUSION: Our study suggests we need to modify the classical diagnostic approach from functional assays followed by candidate- gene or genes sequencing to the firstly parallel genomic screening followed by functional studies.

Analysis of Knowledge, Attitudes, and Prevalence of Hepatitis B and C Seromarkers Among Barbers in Tehran.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health problem in the world. Hairdressers (barbers) are in continuous contact with scissors and blades, and are considered a high-risk group for these infections. OBJECTIVES: The aim of this study was to analyze the prevalence of hepatitis B and C infections in barbers in Tehran and to evaluate their attitudes and knowledge about the occupational risk of these infections. METHODS: Six hundred eleven barbers were included in this study. A group of 556 bakers were also selected from the same regions, as a low-risk control group. Serum levels of hepatitis B surface antigen (HBsAg), HBsAg-specific antibody (HBsAb), hepatitis B core antigen-specific antibody (HBcAb), and hepatitis C virus-specific (anti-HCV) antibody markers were measured with the enzyme-linked immunosorbent assay (ELISA). Participants were interviewed using a questionnaire consisting of four sections: demographic information, awareness, behavior, and personal attitudes. RESULTS: There were no significant differences in the frequency of HBsAg between the two groups. However, the frequency of HCV Ab in barbers was significantly higher than that in bakers (P < 0.005). In addition, the frequency of HBsAb marker in barbers was significantly correlated with increased awareness (P < 0.05) and number of tattoos (P < 0.001). HBcAb marker was significantly correlated with age (P < 0.001) and duration of professional career (P < 0.005). With age, barbers' attitudes improved significantly (P < 0.05). CONCLUSIONS: Being a barber alone is not a potential risk factor for HBV infection, while HCV infection is still an occupational health hazards for barbers. We suggest more extensive case-control studies with regard to rates of hepatitis B and C markers among barbers in other Iranian cities to assess the incidence of hepatitis B and C infections among this population.

Comparison of Oral Lichen Planus and Systemic Lupus Erythematosus in Interleukins Level.

Lichen planus (LP) is a chronic inflammatory mucocutaneous disorder with unknown etiology. Systemic lupus erythematosus (SLE) is known as a prototypic autoimmune disease. Cytokines play a key role in the pathogenesis of both diseases. Various cytokines, such as interleukin 6 (IL-6), interleukin 10 (IL-10), interferon alpha (INF-a), and Tumor Necrosis Factor-alpha (TNF-a) can serve as biomarkers to predict SLE severity and monitor disease activity. In this review, we compare interleukins in oral lichen planus and lupus erythematosus as an autoimmune disease prototype. So, this review may provide insight for researchers in completing the cytokine network in OLP. Among the etiologic factors, the imbalance between Th-1 and Th-2 cytokine production plays an important role in the development of both diseases. By understanding cytokines and immunoregulatory networks of cytokines in these patients, appropriate treatment can be offered. There are many limitations in cytokine studies, which we have described in this article.

A Placebo-Controlled Study of Raloxifene Added to Risperidone in Men with Chronic Schizophrenia.

Selective estrogen receptor modulators (SERMs) such as raloxifene have already shown beneficial effects on negative, positive and general psychopathology symptoms in postmenopausal women with schizophrenia. The purpose of the present investigation was to assess the efficacy of raloxifene as an adjuvant agent in the treatment of men with chronic schizophrenia in an 8-week double-blind and placebo-controlled trial. In a randomized, double-blind and placebo-controlled study, forty-six male patients diagnosed with schizophrenia (DSM-IV-TR), were randomized to either raloxifene (120 mg/day) or placebo in addition to risperidone (6 mg/day) for eight weeks. The assessment was performed using the positive and negative symptom scale (PANSS) at baseline, and at weeks 2, 4, 6 and 8. Extrapyramidal symptom rating scale (ESRS) at baseline, weeks 1, 2, 4, 6, 8 and Hamilton depression rating scale (HDRS) at baseline and week 8 were also used to assess extrapyramidal symptoms and depression simultaneously. Forty-two patients completed the trial. The raloxifene group showed significantly greater improvement on the negative subscale (P<0.001), the general psychopathology subscale (P=0.002) and total PANSS score (P<0.001) in comparison to the placebo group at the endpoint. There was no significant difference in the reduction of positive symptoms score between the two group (P=0.525). Extrapyramidal symptom rating scale and Hamilton depression rating scale and frequency of other adverse effects were comparable between two groups.This study indicates raloxifene as a potential adjunctive treatment strategy for chronic schizophrenia in men.

Lipoid proteinosis: phenotypic heterogeneity in Iranian families with c.507delT mutation in ECM1.

Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis caused by loss-of-function mutations in the ECM1 gene, and previous studies have noted phenotypic variability. In this study, we examined 12 patients representing three Iranian families for clinical manifestations and genotyped them for mutations in ECM1. LP was diagnosed with characteristic mucocutaneous and neurologic manifestations. Five patients were also subjected to magnetic resonance imaging (MRI)/computed tomography (CT) scan of the central nervous system. DNA was isolated from peripheral blood from patients and their clinically unaffected relatives, and mutations in ECM1 were sought by PCR-based amplification of all exons and flanking intronic sequences, followed by bidirectional Sanger sequencing. Significant phenotypic variability in this multisystem disorder, including presence of convulsions and epilepsy in about half of the patients was noted. In most cases, this was associated with calcifications in the brain detected by MRI/CT scans. Genotyping of the affected individuals in three families from the central region of Iran revealed presence of homozygous c.507delT mutation in ECM1, reflecting the observed consanguinity in these families. This large cohort revealed extensive phenotypic variability in individuals with the same mutation in ECM1. This observation suggests a role for genetic and epigenetic as well as environmental modulation of the phenotype. Identification of mutations allows screening of unaffected individuals for presence or absence of this mutation in extended LP families, with implications for genetic counseling.

Novel trends in genetics: transposable elements and their application in medicine.

Forty-five percent of the human genome is composed of Transposable Elements (TEs); therefore, TEs have had an undisputed impact on evolution of the most evolved creature by a very simple mechanism of action.  Scientists have been studying this simple mechanism of action and are currently using it to develop efficient and safe gene delivery systems especially for treatment of diseases. TEs have also been used safely in generating induced Pluripotent Stem Cells (iPSC) for regenerative medicine, which opens the door to a world of possibilities in our approach in trying to wrestle with many challenges in medicine. The PiggyBac (PB) system has yielded more success in generation of induced pluripotent stem cells in regenerative medicine, and the Sleeping Beauty (SB) has been more successful in Gene Therapy. Recent advances are indicative of more good news to come regarding the potential heights of successes achievable by the use of the TE-based systems.