Late Diagnosis of Turner Syndrome in Adulthood;a Case Study from the Endocrinology-Diabetology Nutrition Department of the National Hospital of Pikine Senegal

Introduction: Turner syndrome is a rare genetic disorder characterised by the presence of one X chromosome and the absence of part or all of an X or Y chromosome and patients may experience delayed puberty and infertility. Our study aimed to evaluate the diagnostic delay in our practice and analyze the impact of this diagnostic delay on the effectiveness of patient management. Patients and Methods: Turner syndrome patients were identified from the endocrinology-diabetology nutrition department Database We examined the records of patients in whom the karyotype analysis favoured Turner syndrome. Results: We have selected 5 patients’ records of female patients with Turner syndrome. The mean age was 25, ranging from 19 to 29 years. Primary amenorrhea and characteristic dysmorphic features were observed in all patients. One married patient, who sought consultation for infertility, expressed a desire for pregnancy. Short stature was identified in 3 patients. Primary hypothyroidism and hypertension were respectively found in 1 and 2 patients. Gonadal dysgenesis was noted in 100% of cases. Karyotype analysis revealed monosomy X in 2 patients and mosaic patterns in others. All patients received estrogen-progestin treatment. Antihypertensive therapy was initiated for 2 patients. One patient is on L-thyroxine. In the short term, treatment led to the onset of menstruation after the initial months. Evaluation of treatment efficacy on internal genital organs is yet to be performed. Due to uncertain benefits at this age, growth hormone therapy was not considered for our patients. We provided counseling on assisted reproductive options for couples desiring to conceive. In our study, all patients were placed on estrogen-progestin therapy, and the response appeared favorable. Conclusion: In our practice, the diagnosis of Turner syndrome occurs very late in adulthood, at an age when growth hormone treatment is nearly ineffective. Treatment typically revolves around estrogen-progestin therapy, along with managing other comorbidities such as hypertension and primary hypothyroidism.

Genetics of diabetes

Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic,epigenetic,and environmental variables.It is one of the world's fastestgrowing diseases,with 783 million adults expected to be affected by 2045.Devastating macrovascular consequences(cerebrovascular disease,cardiovascular disease,and peripheral vascular disease)and microvascular complications(like retinopathy,nephropathy,and neuropathy)increase mortality,blindness,kidney failure,and overall quality of life in individuals with diabetes.Clinical risk factors and glycemic management alone cannot predict the development of vascular problems;multiple genetic investigations have revealed a clear hereditary component to both diabetes and its related complications.In the twenty-first century,technological advancements(genome-wide association studies,nextgeneration sequencing,and exome-sequencing)have led to the identification of genetic variants associated with diabetes,however,these variants can only explain a small proportion of the total heritability of the condition.In this review,we address some of the likely explanations for this"missing heritability",for diabetes such as the significance of uncommon variants,gene-environment interactions,and epigenetics.Current discoveries clinical value,management of diabetes,and future research directions are also discussed.

Autophagy and mitophagy as potential therapeutic targets in diabetic heart condition:Harnessing the power of nanotheranostics

Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC),which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies.Despite significant progress in reducing mortality rates from cardiovascular diseases(CVDs),heart failure remains a major cause of increased morbidity among diabetic patients.These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components,and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment.While a variety of conventional diagnostic and therapeutic strategies are available,DHC continues to present a significant challenge.Point-of-care diagnostics,supported by nanobiosensing techniques,offer a promising alternative for these complex scenarios.Although conventional medications have been widely used in DHC patients,they raise several concerns regarding various physiological aspects.Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC,offering a promising approach to deliver drugs beyond the limitations of traditional therapies.This article aims to explore the potential connections between autophagy,mitophagy and DHC,while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.

Constituents of the anti-asthma herbal formula ASHMI^(TM) synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells,and eotaxin by human lung fibroblasts in vitro

OBJECTIVE： Anti-asthma herbal medicine intervention （ASHMITM）, a combination of three tradi- tional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMITM exhibited synergy. METHODS： Effects of ASHMI and its components aqueous extracts of Lingzhi （Ganoderma lucidum）, Kushen （Sophora flavescens） and Gancao （Glycyrrhiza uralensis）, on Th2 cytokine secretion by murine memory Th2 cells （D10.G4.1） and eotaxin-1 secretion by human lung fibroblast （HLF-1） cells were determined by measuring levels in culture supernatants by enzyme- linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters. RESULTS： Individual Lingzhi, Kushen and Gancao extracts and ASHMI （the combination of individual extracts） inhibited production of interleukin （IL）-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration （IC2s） values （mg/mL） forASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50values （mg/mL） for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-l. The interaction indices at IC^0 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC^0 values. All interaction indices were below 1 which indicated synergy. CONCLUSION： By comparing the interaction index values, we find that constituents in ASHMITM synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.

What is the purpose of launching the World Journal of Medical Genetics?

Congratulations to the publisher,members of the editorial board of the journal,all the authors and readers for launching the World Journal of Medical Genetics(WJMG)as a new member of the World series journal family!Following the completion of the Human Genome Project,medical genetic research has seen spectacular progress over the last decade.The number of genes that have been linked to Mendelian human traits has grown exponentially and currently this process is peaking with the access to robust genome-wide sequencing power.The genomics revolution is also seen for elucidation of rare and common DNA variants that increase risk for common disorders.Given this fast progress,there is an increasing need for making the results of genetics and genomics studies rapidly and freely available to the larger community.Thus,the decision for inaugurating this new journal is a timely one.The WJMG is a peer-reviewed,open-access periodical centered in all aspects of medical genetics research,with multidisciplinary coverage:from human phenotype to genetic and genomic mutations and variations to the study of pathological mechanisms.If you want to share new results of your research with a link to medical genetics with your peers,you will find the WJMG a good media to publish your papers!

Current therapeutic modalities and chemopreventive role of natural products in liver cancer:Progress and promise

Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes a significant subtype of liver cancer(approximate75%)and is considered primary liver cancer.Treatment for liver cancer mainly depends on the stage of its progression,where surgery including,hepatectomy and liver transplantation,and ablation and radiotherapy are the prime choice.For advanced liver cancer,various drugs and immunotherapy are used as first-line treatment,whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins.Sorafenib and lenvatinib are first-line therapies,while regorafenib and ramucirumab are secondline therapy.Various metabolic and signaling pathways such as Notch,JAK/STAT,Hippo,TGF-β,and Wnt have played a critical role during HCC progression.Dysbiosis has also been implicated in liver cancer.Drug-induced toxicity is a key obstacle in the treatment of liver cancer,necessitating the development of effective and safe medications,with natural compounds such as resveratrol,curcumin,diallyl sulfide,and others emerging as promising anticancer agents.This review highlights the current status of liver cancer research,signaling pathways,therapeutic targets,current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.

Quantitation of Polydeoxyribonucletides (PDRNs) in Human Placental Extract by Fluorescence Spectroscopy Using Ethidium Bromide

Characterization of an aqueous extract of human placenta, used as a licensed drug for wound healing, leads to the identification of several bioactive components including polydeoxyribonu-cleotides (PDRNs). PDRNs are mixture of DNA fragments of different molecular weight. A spectro-fluorimetric method of quantitation of PDRNs in the aqueous extract of human placenta by using ethidium bromide (EtBr) has been described here. It has been demonstrated by thin layer chromatography (TLC) followed by reversed phase HPLC that EtBr binds specifically with the PDRN fraction of the multi-component extract. The binding specificity of EtBr has been verified by the analysis of emission spectra of the extract. A concentration of 0.29 μg/ml EtBr exhibits a linear range of standard CT-DNA from 0.5 - 5 μg/ml of buffer (R2 = 0.992). The same concentration of EtBr shows a linear range of measurements of placenta extract from 5 - 35 μl/ml of buffer (R2 = 0.976). The points of the curve were the average of three sets where maximum variation observed was ±3%. PDRN content of the extract has been estimated based on the resultant fluorescence emission (after background correction) with respect to the standard calibration curve of calf thymus DNA (CT-DNA). Estimation of PDRN in a large number of batches of placenta extract (n = 100) has been done. The statistical analysis of the estimation was found to be significant and the lower and upper levels of PDRN were 158.30 and 239.03 μg/ml of the extract respectively. This easy-to-use method of estimation of PDRN in multi-component biological extract is reported for the first time. This will help in quantitation of PDRNs for other biological extracts.

CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population

Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Methods: Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22;45.5%), and other five were compound heterozygous for this variant (15/22;68.2%). The other mutations found were p.Q128X (c.721 C>T;2/22), p.S139F (c.755 C>T;4/22) and c.18-21delGACT (p.T7FfsX7;1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.

Neuron-to-astrocyte proteostatic stress signaling in response to tau pathology

Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of cells.This is in particular the case for cells like neurons that cannot self-renew and acquire unique functional properties during their lifetime.Cellular proteostatic stress responses are in place to protect cells from damage in case of proteostatic challenges.The integrated stress response(ISR)is one of the key proteostatic stress responses in the cell(Costa-Mattioli and Walter,2020).The ISR is the downstream convergence point for the four stress-induced eIF2αkinases(EIF2AK1-4)that control stress-regulated protein translation via phosphorylation of the translation factor eIF2α.ISR activation results in a transient reduction of global translation while it concomitantly enhances the translation of specific mRNAs,including that encoding the activating transcription factor 4(ATF4).Together,the translational control mediated by the ISR results in a temporary reduction of the overall protein load and the selectively increased expression of proteins that contribute to restoration of the proteostatic balance.

Trophic factors are essential for the survival of grafted oligodendrocyte progenitors and for neuroprotection after perinatal excitotoxicity

The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent causes of acquired myelin deficiency in the human neonate leading to cerebral palsy and cognitive impairment.In the developing brain,oligodendrocyte(OL)maturation occurs perinatally,and immature OLs are particularly vulnerable.Cell replacement therapy is often considered a viable option to replace progenitors that die due to glutamate excitotoxicity.We previously reported directed specification and mobilization of endogenous committed and uncommitted neural progenitors by the combination of transferrin and insulin growth factor 1(TSC1).Here,considering cell replacement and integration as therapeutic goals,we examined if OL progenitors(OLPs)grafted into the brain parenchyma of mice that were subjected to an excitotoxic insult could rescue white matter injury.For that purpose,we used a well-established model of glutamate excitotoxic injury.Four-day-old mice received a single intraparenchymal injection of the glutamate receptor agonist N-methyl-D-aspartate alone or in conjunction with TSC1 in the presence or absence of OLPs grafted into the brain parenchyma.Energetics and expression of stress proteins and OL developmental specific markers were examined.A comparison of the proteomic profile per treatment was also ascertained.We found that OLPs did not survive in the excitotoxic environment when grafted alone.In contrast,when combined with TSC1,survival and integration of grafted OLPs was observed.Further,energy metabolism in OLPs was significantly increased by N-methyl-D-aspartate and modulated by TSC1.The proteomic profile after the various treatments showed elevated ubiquitination and stress/heat shock protein 90 in response to N-methyl-D-aspartate.These changes were reversed in the presence of TSC1 and ubiquitination was decreased.The results obtained in this pre-clinical study indicate that the use of a combinatorial intervention including both trophic support and healthy OLPs constitutes a promising approach for long-term survival and successful graft integration.We established optimal conditioning of the host brain environment to promote long-term survival and integration of grafted OLPs into an inflamed neonate host brain.Experimental procedures were performed under the United States Public Health Service Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care Committee at(UCLA)(ARC#1992-034-61)on July 1,2010.

NAT2＊6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis

AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.

Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population:Role of serine protease inhibitor Kazal 1type and alcohol

AIM： To test the hypothesis that calcium sensing receptor （CASR） polymorphisms are associated with chronic pancreatitis （CP）, and to determine whether serine protease inhibitor Kazal 1type （SPINK1） N34S or alcohol are necessary co-factors in its etiology. METHODS： Initially, 115 subjects with pancreatitis and 66 controls were evaluated, of whom 57 patients and 21 controls were predetermined to carry the high-risk SPINK1 N34S polymorphism. We sequenced CASR gene exons 2, 3, 4, 5 and 7, areas containing the majority of reported polymorphisms and novel mutations. Based on the initial results, we added 223 patients and 239 controls to analyze three common nonsynonymous single nucleotide polymorphisms （SNPs） in exon 7 （A986S, R990G, and Q1011E）. RESULTS： The CASR exon 7 R990G polyrnorphism was significantly associated with CP （OR, 2.01; 95% CI, 1.12-3.59; P = 0.015）. The association between CASR R990G and CP was stronger in subjects who reported moderate or heavy alcohol consumption （OR, 3.12; 95% CI, 1.14-9.13; P = 0.018）. There was no association between the various CASR genotypes and SPINK1 N34S in pancreatitis. None of the novel CASR polymorphisms reported from Germany and India was detected. CONCLUSION： Our United States-based study confirmed an association of CASR and CP and for the first time demonstrated that CASR R990G is a significant risk factor for CP. We also conclude that the risk of CP with CASR R990G is increased in subjects with moderate to heavy alcohol consumption.

Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese

AIM： To examine an association between the cytotoxic Tlymphocyte antigen 4 （CTLA4） gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis （UC） and Crohn＇s disease （CD） in the Japanese.METHODS： We studied 108 patients with UC, 79 patients with CD, and 200 sex-matched healthy controls, with respect to three single nucleotide polymorphisms （SNPs） in CTLA4, such as C-318T in the promoter region, A＋49 Gin exon 1 and G＋6230A in the 3＇ untranslated region （3＇-UTR） by a PCR-restriction fragment length polymorphism method, and to an （AT）, repeat polymorphism in 3＇-UTR by fragment analysis with fluorescence-labeling on denaturing sequence gels. Frequency of alleles and genotypes and their distribution were compared statistically between patients and controls and among subgroups of patients, using X^2 and Fisher exact tests.RESULTS： The frequency of ＂A/A＂ genotype at the G＋6230A SNP site was statistically lower in UC patients than in controls （3.7% vs 11.0%, P = 0.047, odds ratio （OR） = 0.311）. Moreover, the frequency of ＂G/G＂ genotype at the A＋49G SNP site was significantly higher in CD patients with fistula （48.6%） than those without it （26.2%）（P = 0.0388, OR=2.67）.CONCLUSION： The results suggest that CTLA4 located at 2q33 is a determinant of UC and responsible for fistula formation in CD in the Japanese.

Effects of Aqueous Extract of Plumbago zeylanica L. in the Reversal of DMN-induced Hepatic Fibrosis in Rat

[ Objectives ] This study was conducted to evaluate the action of the aqueous extract of a medicinal plant Plumbago zeylanica L. in the reversal of dime- thylnitrosamine （DMN） -induced hepatic fibrosis in rats, and to provide a scientific basis for the utilization of P. zeylanica in treatment of hepatic fibrosis. [Meth- ods ] Hepatic fibrosis in rats was induced by intraperitoneal injection of DMN. The rats were then given the aqueous extract of P. zeylanica at high, medium or low concentration by garage for five weeks. Serum level of alanine aminotransferase （ALT） was determined by lactate dehydrogenase （LDH）-release assay, and serum level of aspartate transaminase （AST） was measured by UV-malate dehydrogenase （MDH） assay. Serum levels of total bilirubin （TBIL）, direct bilirubin （DBIL） and indirect bilirubin （1BIL） were measured by vanadate oxidation assay. Four indices of hepatic fibrosis （hyaluronic acid, laminin, procollagen type III and colla- gen type IV） were determined by radioimmunoassay （RIA） assay. Morphological damage of liver tissue was observed by hematoxylin-eosin staining （H＆E stai- ning）. Immunohistochemical staining was performed to determine the location and area of deposited collagen type I, collagen type III and ct-smeoth muscle actin （a-SMA） in liver tissue. [ Results] Compared with the negative control （rats with diseased fiver and untreated with P. zeylanica aqueous extract）, the serum lev- els of ALT, AST, TBIL, DBIL and IBIL were significantly decreased by P. zeylanica aqueous extract; the levels of the four serum indices of hepatic fibrosis were also obviously reduced. H＆E staining showed that hepatic fibrosis in rats was obviously inhibited or even reversed by P. zeylanica aqueous extract. Immunohisto- chemical staining proved that the aqueous extract of P. zeylanica significantly reduced the area and coloration of collagen type I, collagen type III and ct-SMA in rat liver. [ Conclusions] The aqueous extract of P. zeylanica has a definite effect in reversal of DMN-indueed hepatic fibrosis in rat by promoting the recovery of liver function, reversal of histopathological changes and reducing fibrotic collagen.

Phosphatidylserine improves axonal transport by inhibition of HDAC and has potential in treatment of neurodegenerative diseases

Familial dysautonomia （FD） is a rare children neurodegenerative disease caused due to a point mutation in the IKBKAP gene that results in decreased IKK complex-associated protein （IKAP） protein production. The disease affects mostly the dorsal root ganglion （DRG） and the sympathetic ganglion. Recently, we found that the molecular mechanisms underlying neurodegeneration in FD patients are defects in axonal transport of nerve growth factors and microtubule stability in the DRG. Neurons are highly polarized cells with very long axons. In order to survive and maintain proper function, neurons depend on transport of proteins and other cellular components from the neuronal body along the axons. We further demonstrated that IKAP is necessary for axon maintenance and showed that phosphatidylserine acts as an HDAC6 inhib- itor to rescue neuronal function in FD cells. In this review, we will highlight our latest research findings.

Crohn's disease in Japanese is associated with a SNP-haplotype of N-acetyltransferase 2 gene

AIM： To investigate the frequency and distribution of /V-acetyltransferase 2 （NAT2） and uridine 5＇-diphosphate （UDP）-glucuronosyltransferase 1A7 （UGT1A7） genes in patients with ulcerative colitis （UC） and Crohn＇s disease （CD）. METHODS： Frequencies and distributions of IVAT2 and UGT1A7SNPs as well as their haplotypes were investigated in 95 patients with UC, 60 patients with CD, and 200 gender-matched, unrelated, healthy, control volunteers by PCR-restriction fragment length polymorphism （RFLP）, PCR-denaturing high-performance liquid chromatography （DHPLC）, and direct DNA sequencing. RESULTS： Multiple logistic regression analysis revealed that the frequency of haplotype, NAT2＊7B, significantly increased in CD patients, compared to that in controls （P= 0.0130, OR = 2.802, 95%CI = 1.243-6.316）. However, there was no association between NAT2 haplotypes and UC, or between any UGT1A7haplotypes and inflammatory bowel disease （IBD）. CONCLUSION： It is likely that the NAT2 gene is one ofthe determinants for CD in Japanese. Alternatively, a new CD determinant may exist in the 8p22 region, where NAT2 is located.

Electrophysiology and genetic testing in the precision medicine of congenital deafness:A review

Background:Congenital hearing loss is remarkably heterogeneous,with over 130 deafness genes and thousands of variants,making for innumerable genotype/phenotype combinations.Understanding both the pathophysiology of hearing loss and molecular site of lesion along the auditory pathway permits for significantly individualized counseling.Electrophysiologic techniques such as electrocochleography(ECochG)and electrically-evoked compound action potentials(eCAP)are being studied to localize pathology and estimate residual cochlear vs.neural health.This review describes the expanding roles of genetic and electrophysiologic evaluation in the precision medicine of congenital hearing loss.The basics of genetic mutations in hearing loss and electrophysiologic testing(ECochG and eCAP)are reviewed,and how they complement each other in the diagnostics and prognostication of hearing outcomes.Used together,these measures improve the understanding of insults to the auditory system,allowing for individualized counseling for CI candidacy/outcomes or other habilitation strategies.Conclusion:Despite tremendous discovery in deafness genes,the effects of individual genes on neural function remain poorly understood.Bridging the understanding between molecular genotype and neural and functional phenotype is paramount to interpreting genetic results in clinical practice.The future hearing healthcare provider must consolidate an ever-increasing amount of genetic and phenotypic information in the precision medicine of hearing loss.

Homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene

Dear Sir,Iam Haiba Kaul,from the Department of Biochemistry,University of Health Sciences,Lahore,Pakistan.I write to present a study of oculocutaneous albinism（OCA）in consanguineous Pakistani families.OCA is a genetic defect of melanin biosynthesis that mainly affects eyes,skin and hair.

Changing paradigm of cancer therapy：precision medicine by next-generation sequencing

Precision medicine aims to identify the right drug, for the right patient, at the right dose, at the right time, which is particularly important in cancer therapy. Problems such as the variability of treatment response and resistance to medication have been longstanding challenges in oncology, especially for development of new medications. Solid tumors, unlike hematologic malignancies or brain tumors, are remarkably diverse in their cellular origins and developmental timing. The ability of next-generation sequencing(NGS) to analyze the comprehensive landscape of genetic alterations brings promises to diseases that have a highly complex and heterogeneous genetic composition such as cancer. Here we provide an overview of how NGS is able to facilitate precision medicine and change the paradigm of cancer therapy, especially for solid tumors, through technical advancements, molecular diagnosis, response monitoring and clinical trials.

Genetic evaluation and testing for hereditary forms of cancer in the era of next-generation sequencing

The introduction of next-generation sequencing(NGS) technology in testing for hereditary cancer susceptibility allows testing of multiple cancer susceptibility genes simultaneously. While there are many potential benefits to utilizing this technology in the hereditary cancer clinic, including efficiency of time and cost, there are also important limitations that must be considered. The best panel for the given clinical situation should be selected to minimize the number of variants of unknown significance. The inclusion in panels of low penetrance or newly identified genes without specific actionability can be problematic for interpretation.Genetic counselors are an essential part of the hereditary cancer risk assessment team, helping the medical team select the most appropriate test and interpret the often complex results. Genetic counselors obtain an extended family history, counsel patients on the available tests and the potential implications of results for themselves and their family members(pre-test counseling), explain to patients the implications of the test results(post-test counseling), and assist in testing family members at risk.