Application of Clinical Genetics最新文献

{"title":"Candidate Gene Analysis Of Alopecia Areata In Jordanian Population Of Arab Descent: A Case–Control Study","authors":"L. Al-Eitan, Rawan O. Al Momani, Khalid K Al Momani, Ahmad M Al Warawrah, Hanan A. Aljamal, M. Alghamdi, A. Muhanna, Firas A. Al-qarqaz","doi":"10.2147/TACG.S226664","DOIUrl":"https://doi.org/10.2147/TACG.S226664","url":null,"abstract":"Background Alopecia areata (AA) is a non-cicatricial patchy hair loss on the scalp, face or other parts of the body. AA was found to be responsive to immunosuppressive therapies, a finding that supports an autoimmune basis for the disease. Several genetic studies have shown the significance of immunological factors as key genetic components in AA. Objective In this study, we aimed to investigate the genetic association of 7 single-nucleotide polymorphisms (SNPs) within five candidate genes including TAP1, CXCL1, CXCL2, HSPA1B, and TNFα with AA susceptibility in the Jordanian Arab population. Methods A case–control genetic association study conducted in 152 patients and 150 healthy individuals was performed using the sequenom MassARRAY system (iPLEX GOLD) to genotype the selected SNPs. Results rs1800629 SNP of the TNFα gene was significantly associated with AA in the heterozygous and rare homozygous genotypes (P=0.022 and P=0.0079, respectively) with no linkage of the TAP1, CXCL1, CXCL2 and HSPA1B variants. Conclusion This is the first study of its kind among the Jordanian population providing evidence of genetic association of the TNFα with AA susceptibility. Further genetic studies on Arab descent including other variants are required to clarify and strengthen the association of these genes with susceptibility to develop AA.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"221 - 228"},"PeriodicalIF":3.1,"publicationDate":"2019-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S226664","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45577408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLC22A1 And ATM Genes Polymorphisms Are Associated With The Risk Of Type 2 Diabetes Mellitus In Western Saudi Arabia: A Case-Control Study","authors":"Rana M Altall, S. Qusti, Najlaa Filimban, A. Alhozali, N. A. Alotaibi, A. Dallol, A. Chaudhary, S. Bakhashab","doi":"10.2147/TACG.S229952","DOIUrl":"https://doi.org/10.2147/TACG.S229952","url":null,"abstract":"Introduction Type 2 diabetes mellitus (T2DM) is a major global health problem that is progressively affected by genetic and environmental factors. The aim of this study is to determine the influence of solute carrier family 22 member 1 (SLC22A1) rs628031 and rs461473, and ataxia telangiectasia mutated (ATM) rs11212617 polymorphisms on the risk of T2DM in Saudi Arabia by considering many parameters associated with glycemic control of T2DM, such as body mass index (BMI), fasting blood glucose, glycated hemoglobin (HbA1c), and triglyceride. Methods In a case-control study, genomic DNA from controls and diabetic groups was isolated and genotyped for each single-nucleotide polymorphism. Results There were significant correlations between T2DM and both BMI and HbA1c. Significant associations between G/G and A/G genotypes of rs628031 and rs461473 variants of SLC22A1 and high levels of HbA1c were detected. Therefore, G was predicted to be the risk allele among the assessed SLC22A1 variants. A significant correlation was observed between A/A and A/C genotypes of the rs11212617 polymorphism of ATM and elevated HbA1c. Relative risk calculation confirmed A to be the risk allele in the T2DM population. Conclusion Our study showed the risk of the assessed SLC22A1 and ATM variants on glycemic control parameters in diabetic patients.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"213 - 219"},"PeriodicalIF":3.1,"publicationDate":"2019-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S229952","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43610477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM5α 136Q, CCR5 Promoter 59029G And CCR264I Alleles Impact The Progression Of HIV In Children And Adolescents.","authors":"Béatrice Dambaya, Céline Nguefeu Nkenfou, Linda Mekue, Georges Této, Nicole Ngoufack, Georgia Ambada, Njiokou Flobert, Vittorio Colizzi, Ndjolo Alexis","doi":"10.2147/TACG.S205335","DOIUrl":"10.2147/TACG.S205335","url":null,"abstract":"<p><strong>Background: </strong>Children show various degrees of vulnerability regarding HIV infection and disease progression. This disparity presents challenges for the follow-up of infected children. Here we investigated reasons behind this variability focusing on some host-related HIV genes.</p><p><strong>Methods: </strong>We screened 570 Cameroonian children and adolescents, aged 1 to 19 years old. Among them, 137 were followed over 4 years, from 2010 to 2015. Upon signing a proxy consent, children and adolescents were classified according to their age, CD4 count, viral load and clinical symptoms as long-term non-progressors (LTNP), slow progressors (SP) and rapid progressors (RP). Their blood was collected every 6 months and used for biological and host genetic polymorphism analyses. Five genes were genotyped: <i>Trim5α (R136Q), CCR5</i> promoter <i>59029G, CCR2-64I, SDF 3'A</i> and <i>CCR5-Δ32</i>. Exposed non-infected (HEU) and unexposed HIV negative children (HNEU) were recruited as control groups.</p><p><strong>Results: </strong>Among the 5 genes studied, the protective allele of Trim5α (R136Q) was present in all LTNP and in 72.34% and 2.56% of SP and RP, respectively (p<0.0001). The CCR5 promoter 59029G/G was also more present in LTNP and SP than in RP (p=0.02; p=0.04). The protective CCR2-64I homozygous genotype was almost absent in all groups, only the heterozygous genotype was present with a significant difference between RP vs SP (p=0.0001), and SP vs LTNP (p=0.0002). The CCR2-∆32 was completely absent either as homozygous or heterozygous genotype. It was a monomorphic allele. SDF 3'A was almost present as homozygous wild-type genotype in our study population and was associated neither to disease acquisition nor to disease progression.</p><p><strong>Conclusion: </strong>Among the 5 genes described in the study, Trim 5α (R136Q), CCR5 promoter 59029G and CCR2V64I alleles were associated to the progression of HIV infection in children and adolescents.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"203-211"},"PeriodicalIF":2.6,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42679472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update On The Clinical Perspectives And Care Of The Child With 47,XXY (Klinefelter Syndrome).","authors":"Carole A Samango-Sprouse,&nbsp;Debra R Counts,&nbsp;Selena L Tran,&nbsp;Patricia C Lasutschinkow,&nbsp;Grace F Porter,&nbsp;Andrea L Gropman","doi":"10.2147/TACG.S180450","DOIUrl":"https://doi.org/10.2147/TACG.S180450","url":null,"abstract":"<p><p>47,XXY (Klinefelter syndrome [KS]) is the most common sex chromosomal aneuploidy (1:660), yet, despite this, only 25% of the males are ever diagnosed. Males with 47,XXY present with characteristic symptoms throughout their lifetime with typical physical and neurodevelopmental manifestations focused in growth, cognitive development, endocrine function, and reproduction. Studies have demonstrated that optimal outcomes are dependent on early detection combined with consistent and targeted neurodevelopmental treatment throughout the lifespan. During infancy and into the preschool years, individuals with 47,XXY commonly face deficits in growth and development in the areas of early hormonal, motor, speech, and behavioral development. As they transition into school, the primary neurodevelopmental concerns include language difficulty, executive dysfunction, behavior, and learning and reading deficits. Adults with 47,XXY often present with taller than average height, low levels of fertility, azoospermia, and elevated gonadotropin levels. These presentations may persist from early childhood through adulthood but can be mitigated by appropriate interventions. Early neurodevelopmental and hormonal treatment has been shown to have a minimizing effect on the physical and neurodevelopmental manifestations in individuals with 47,XXY. With innovative and current research studies, the features common to the neurodevelopmental profile of 47,XXY have been further expanded and defined. Further research is necessary to elucidate and understand the relationship between the brain, behavior, and the phenotypic profile of 47,XXY.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 ","pages":"191-202"},"PeriodicalIF":3.1,"publicationDate":"2019-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S180450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Analysis Of ABCA1 Gene Of Primary Glaucoma In Jordanian Arab Population","authors":"R. Alkhatib, Nada Abudhaim, L. Al-Eitan, N. Abdo, A. Alqudah, Hatem A. Aman","doi":"10.2147/TACG.S213818","DOIUrl":"https://doi.org/10.2147/TACG.S213818","url":null,"abstract":"Background Glaucoma is a neurodegenerative disease that leads to progressive loss of retinal ganglion cells, causing irreversible visual field defects. At the present time, glaucoma is clinically defined but the exact etiology is unknown. The aim of this study is to genotype rs2472493 and rs2487032 SNIPs within ABCA1 gene in 52 Jordanian Arab patients with primary glaucoma and 96 control subjects, and also to investigate the genetic association of these SNPs with primary glaucoma. Methods DNA was extracted from both patients and controls according to a well-established procedure. Then, DNA was amplified by PCR using specific primers for this gene. Analysis of polymorphisms was carried out by using DNA sequencing genotyping method. Results The results showed that the two SNPs (rs2472493 and rs2487032) located upstream of ABCA1 gene have no significant associations with primary glaucoma disorder (P > 0.05). Conclusion This study is the first of its kind to reveal no genetic association between ABCA1 gene and primary glaucoma disorder in Jordanian population of Arab descent.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"181 - 189"},"PeriodicalIF":3.1,"publicationDate":"2019-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S213818","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47583181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Therapy For Beta-Thalassemia: Updated Perspectives","authors":"Garyfalia Karponi, Nikolaos Zogas","doi":"10.2147/TACG.S178546","DOIUrl":"https://doi.org/10.2147/TACG.S178546","url":null,"abstract":"Abstract Allogeneic hematopoietic stem cell transplantation was until very recently, the only permanent curative option available for patients suffering from transfusion-dependent beta-thalassemia. Gene therapy, by autologous transplantation of genetically modified hematopoietic stem cells, currently represents a novel therapeutic promise, after many years of extensive preclinical research for the optimization of gene transfer protocols. Nowadays, clinical trials being held on a worldwide setting, have demonstrated that, by re-establishing effective hemoglobin production, patients may be rendered transfusion- and chelation-independent and evade the immunological complications that normally accompany allogeneic hematopoietic stem cell transplantation. The present review will offer a retrospective scope of the long way paved towards successful implementation of gene therapy for beta-thalassemia, and will pinpoint the latest strategies employed to increase globin expression that extend beyond the classic transgene addition perspective. A thorough search was performed using Pubmed in order to identify studies that provide a proof of principle on the aforementioned topic at a preclinical and clinical level. Inclusion criteria also regarded gene transfer technologies of the past two decades, as well as publications outlining the pitfalls that precluded earlier successful implementation of gene therapy for beta-thalassemia. Overall, after decades of research, that included both successes and pitfalls, the path towards a permanent, donor-irrespective cure for beta-thalassemia patients is steadily becoming a realistic approach.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"167 - 180"},"PeriodicalIF":3.1,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S178546","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48234266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketogenic diet in ATAD3A mutation carriers may not improve cerebellar atrophy but some clinical features [Letter]","authors":"J. Finsterer","doi":"10.2147/TACG.S221407","DOIUrl":"https://doi.org/10.2147/TACG.S221407","url":null,"abstract":"Krankenanstalt Rudolfstiftung, Messerli Institute, Vienna, Austria Dear editor With interest I read the article by Madhoun et al about a 4.5-year-old female with multisystem mitochondrial disorder (MID) due to the variant c.251T>C in the ATAD3A gene. The patient was reported to have profited from the ketogenic diet (KD) by slowing the progression of cerebellar atrophy, and improving vitality, interaction, moaning, carrying, tremor, and weakness. I have the following comments and concerns. It is quite unlikely that the cerebellar volume increased upon application of the KD. More likely is that the increase in the relative sagittal length of the cerebellum was due to variability of repeated measurements or simply due to the growing cerebellum in this developing child. Potential volumetric changes can be only confirmed by investigating a series of patients but not by assessing a single case. The tremor in the patient was attributed to Parkinsonism most likely upon the phenotype as a hand pill rolling tremor. We should be informed about the DatScan results, if the tremor responded to L-DOPA, and if there were any other stigmata of Parkinsonism in this patient. More likely than Parkinson's tremor is a cerebellar tremor in the light of progressive cerebellar atrophy. A hand pill rolling tremor may also occur with a cerebellar syndrome. MRI in figure 1 suggests that there was also atrophy of the spinal cord. It is conceivable that muscle weakness in the described patient was attributable to involvement of the anterior horn cells. Were there any indications for neuronopathy in the presented patient? Though optic atrophy may be a feature of ATAD3A mutations, it was not reported as a feature of the index case. Optic atrophy may be subtle and not visible on ophthalmologic or imaging investigations but only on functional tests. Thus, we should be informed if latency and amplitude of visually evoked potentials were prolonged respectively reduced. We should be informed if muscle weakness was attributed to affection of the central nervous system or due to myopathy. It should be mentioned if deep tendon reflexes were reduced or exaggerated. A normal needle EMG does not exclude myopathy. Since seizures have been reported as a phenotypic feature of ATAD3A mutations, we should be informed about the history in this regards and the EEG findings. Correspondence: Josef Finsterer Krankenanstalt Rudolfstiftung, Messerli Institute, Postfach 20, 1180 Vienna, Austria Tel +43 1 711 657 2085 Fax +43 17 1165 Email fifigs1@yahoo.de The Application of Clinical Genetics Dovepress open access to scientific and medical research","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"161 - 162"},"PeriodicalIF":3.1,"publicationDate":"2019-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S221407","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44908136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymorphisms of <i>CYP2C9*2, CYP2C9*3</i> and <i>VKORC1</i> genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.","authors":"Maria Mariana Barros Melo da Silveira, Leiliandry de Araújo Melo, Filipe Maia Ferreira Gomes, Leonardo José de Cupertino Barreto da Rocha Andrade, Isabela Paulino Serur, Isabelle Cecília de Vasconcellos Piscoya, Raposo Marina Gueiros, Kleyton Palmeira do Ó, Raul Emídio de Lima, Victor Arthur Eulálio Brasileiro, Luydson Richardson Silva Vasconcelos, Dário Celestino Sobral Filho","doi":"10.2147/TACG.S197316","DOIUrl":"10.2147/TACG.S197316","url":null,"abstract":"<p><strong>Introduction: </strong>Warfarin continues to be the most widely used anticoagulant in clinical practice around the world for the prevention of thromboembolic events in patients with atrial fibrillation (AF). The evaluation of the quality of anticoagulation control, estimated by time in therapeutic range (TTR), is accepted as a good method to evaluate the quality of anticoagulation. The variability of TTR can be explained by the presence of variants of the <i>CYP2C9</i> and <i>VKORC1</i> genes.</p><p><strong>Methods: </strong>This study examined the association between polymorphisms of the <i>CYP2C9</i> and <i>VKORC1</i> genes and control of oral anticoagulation, through TTR, in patients with AF. A cross-sectional study was conducted within a cohort follow-up. The study comprised of 317 patients with AF, using warfarin, who were followed up for one year. The genotyping of genes <i>CYP2C9</i> (rs1057910), (rs1799853) and <i>VKORC1</i> (rs923231) was performed by PCR in real time, using TaqMan probes.</p><p><strong>Results: </strong>Patients who had variant genotypes for the <i>CYP2C9*3</i> gene (rs1057910) presented higher TTR (TTR 81-100%) when compared to when compared to the <45% and 46-60% TTR groups (<i>p</i>=0.005 and <i>p</i>=0.002, respectively). Regarding <i>VKORC1</i> (rs923231), patients who had the variant genotype for the <i>VKORC1</i> (rs923231) gene also presented a higher TTR (TTR 81-100%), when when compared to the <45% and 46-60% TTR groups (<i>p</i>=0.005 and <i>p</i>=0.004, respectively). In a multivariate model, <i>VKORC1</i> (rs923231) remained associated for comparisons with the TTR groups (<45% vs 81-100% groups, <i>p</i>=0.01; and 46-60% vs 81-100% groups, <i>p</i>=0.01).</p><p><strong>Conclusion: </strong>The genotypes of the <i>CYP2C9*3</i> (AA) and <i>VKORC1</i> -1639 (GG) genes were associated with the worst quality of anticoagulation control (TTR) in patients with AF using warfarin in the northeast of Brazil.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 ","pages":"151-159"},"PeriodicalIF":2.6,"publicationDate":"2019-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/08/84/tacg-12-151.PMC6684853.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketogenic diet attenuates cerebellar atrophy progression in a subject with a biallelic variant at the ATAD3A locus [Response to Letter]","authors":"A. Al Madhoun, Fahad Alnaser, Motasem Melhem, R. Nizam, Tala Al-Dabbous, F. Al-Mulla","doi":"10.2147/TACG.S224520","DOIUrl":"https://doi.org/10.2147/TACG.S224520","url":null,"abstract":"Ashraf Al Madhoun Fahad Alnaser Motasem Melhem Rasheeba Nizam Tala Al-Dabbous Fahd Al-Mulla 1Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman, 15462 Kuwait City, Kuwait; 2Animal and Imaging Core Facility Department, Dasman Diabetes Institute, Dasman, 15462 Kuwait City, Kuwait; 3Radiology Department, Ibn Sina Hospital, Ministry of Health, Kuwait City, Kuwait; 4Bayt Abdullah Children’s Hospice, NBK Children’s Cancer Hospital, Al-Adan ICU, Kuwait City, Kuwait Dear editor It is with great interest to read the comments of Dr. Josef Finsterer on our recent article, “Ketogenic diet attenuates cerebellar atrophy progression in a subject with a biallelic variant at the ATAD3A locus by Al Madhoun et al, 2019,” which has received a substantial article-level metrics and respond to the queries raised single nucleotide polymorphisms and deletion mutations within ATAD3 are lethal at embryonic stage or postnatally and the few survivors are living with low quality of life. Accordingly, ATAD3 genotyping enable prediction of genotype/phenotype relationship. Desai et al (2017) associated ATAD3 function with cholesterol homeostasis and maintenance of the mitochondrial genome stability. We thought that Ketogenic Diet (KD) may modulate mitochondrial biogenesis especially that it has proven efficacy in mitochondriopathies-mediated neurological disorders. Thus, it is not unrealistic to include KD treatment in a disease that is caused by ATAD3 gene mutations. The girl described in our paper is unique. She has been clinically evaluated extensively in Canada, but unfortunately, the family was not given a formal diagnosis. We diagnosed her with Harel-Yoon syndrome after discovering a novel pathogenic missense homozygous mutation in the ATAD3 gene (rs546711654 c.251C&gt;T; p.Thr84Met). Globally, the variant allele frequency of rs546711654 is 0.0002 (https://www.ncbi.nlm.nih.gov/clinvar/variation/452865/). This information means that the disease is rare and therefore it is not possible to study other children harboring the same mutation. In response to KD, we never claimed an increase in the relative sagittal length of the cerebellum. But rather, an obvious slowing of her cerebellar atrophy. The KD was applied between the 2nd and 3rd MRI examination at the age of 4 and 5.5 years old. It has been reported that KD lowers the blood pH, increases ATP by shifting from glucoseto ketone-based metabolism. Although all body tissues are influenced by KD, the most prominent effect is on the nervous system activities. Accordingly, we do not exclude a positive effect on the muscle function. KD increases mitochondrial biogenesis. We agree that a real-effect of KD can only be assessed reliably in double-blind randomized clinical trials, but this is Correspondence: Fahd Al-Mulla Head of Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman, 15462 Kuwait City, Kuwait Tel +9 652 224 2999 Ext. 2211 Email fahd@al-mulla.org The Application of Clinical Gene","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"163 - 165"},"PeriodicalIF":3.1,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S224520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47382108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First report case with negative genetic study (array CGH, exome sequencing) in patients with vertical transmission of Zika virus infection and associated brain abnormalities","authors":"E. Candelo, G. Caicedo, F. Rosso, A. Ballesteros, Jaime Orrego, L. E. Escobar, P. Lapunzina, J. Nevado, H. Pachajoa","doi":"10.2147/TACG.S190661","DOIUrl":"https://doi.org/10.2147/TACG.S190661","url":null,"abstract":"Introduction Zika virus (ZIKV) is a little-known emerging mosquito-borne flavivirus. The perinatal ZIKV infection was associated with birth defects during the Brazilian outbreak. There was an increased risk of intrauterine transmission of the virus and a marked increase in the number of newborns with microcephaly. We report on two such cases. Case Report The first case was a 25-year-old pregnant woman from Colombia who became acutely ill with general symptoms during the tenth week of gestation, followed by severe generalized itching and maculopapular rash for approximately five days. This case was reported during the epidemic stage of the ZIKV infection in Colombia. At 23.3 gestational weeks, ultrasonography showed abnormal intracranial anatomy with cerebral ventriculomegaly, microcephaly, and parenchymal calcification. Given the grave prognosis, the patient elected to terminate the pregnancy at 25 gestational weeks. The second case was a 24-year-old pregnant woman who became acutely ill during the 17th week of gestation, which corresponded with the ZIKV epidemic in Colombia. At 30.5 gestational weeks, ultrasonography showed isolated fetal cerebral ventriculomegaly. We detected ZIKV in the amniotic fluid; however, the virus was not detected in the urine or serum of the mother or fetus. Tests for dengue virus, chikungunya virus, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, HIV, hepatitis B and C, and parvovirus B19 were all negative. Different samples obtained from the placenta, amniotic liquid, and cerebrospinal fluid were positive for viral isolation of ZIKV RNA using TaqMan RT-PCR. Additionally, the parents and fetuses were tested for genetic diseases using whole exome sequencing and array CGH to rule out possible genetic syndromes that produce these congenital abnormalities. Conclusion These were the first cases in Colombia to show early vertical transmission of ZIKV and the first cases associated with congenital cerebral abnormalities in which molecular, infectious, and genomic tests were performed.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"141 - 150"},"PeriodicalIF":3.1,"publicationDate":"2019-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S190661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45975542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}