Implications of genetic testing and informed consent before and after genetic testing in individuals with cancer

Recent advancements in next generation sequencing have allowed for genetic information become more readily available in the clinical setting for those affected by cancer and by treating clinicians.Given the lack of access to geneticists,medical oncologists and other treating physicians have begun ordering and interpreting genetic tests for individuals with cancer through the process of"mainstreaming".While this process has allowed for quicker access to genetic tests,the process of"mainstreaming"has also brought several challenges including the dissemination of variants of unknown significance results,ordering of appropriate tests,and accurate interpretation of genetic results with appropriate followup testing and interventions.In this editorial,we seek to explore the process of informed consent of individuals before obtaining genetic testing and offer potential solutions to optimize the informed consent process including categorization of results as well as a layered consent model.

Advances of Genetic Testing Technology in Etiology Diagnosis of Recurrent Spontaneous Abortion

Recurrent spontaneous abortion (RSA) is a complex and heterogeneous disorder with multiple etiologies. Genetic factors are thought to play an important role in the etiology of RSA. With recent advances in genetic testing technologies, there has been an increasing interest in using these tools to diagnose the etiology of RSA. This review discusses the different types of genetic testing methods, such as karyotyping, chromosomal microarray analysis, next-generation sequencing, and their applications in the diagnosis of the etiology RSA. The use of genetic testing in the diagnosis of RSA has the potential to improve the accuracy of diagnosis and the understanding of the underlying mechanisms of the disorder, which could lead to better management and treatment of affected individuals.

Repeated pregnancy losses with multiple aneuploidies and major genomic imbalance:A case report

Rationale:If one of the partners is having balanced autosomal translocation,it is usually observed that the offspring inherit either normal chromosomes,balanced translocation identical to one of the parent or unbalanced chromosomal rearrangements of the same parental chromosome having translocation.Concern:A unique case presented with history of 8 miscarriages for genetic counseling.The last abortus material evaluation showed monosomy of chromosome X(Turner syndrome)in all the analyzed cells.There was a history of infertility and also repeated second trimester abortions on the paternal side.On the maternal side,there was a history of intellectual disability.Diagnose:History of repeated abnormal pregnancy outcomes.Wife’s karyotype is normal;however,husband shows translocation between chromosome 4 and 22.Intervention:Peripheral blood sample around 3 mL was collected for karyotype.Embryo biopsy was done and DNA was extracted and processed for whole exome sequencing.Outcomes:Wife’s karyotype is normal and husband has translocation between chromosome 4 and 22.Surprisingly,the entire pregnancy outcome including embryo screening has different,complete or partial aneuploidies of chromosomes other than chromosome 4 and 22.Main lesson:Though the translocation in one of the parent is balanced,we have to think beyond traditional ways for evaluating a couple with repeated pregnancy loss as we cannot predict the errors at cell division.Option of in vitro fertilization and preimplantation genetic diagnosis in couples having balanced translocations should be discussed so that early intervention can prevent the agony of pregnancy loss.

Diagnosis and management of benign recurrent intrahepatic cholestasis and psychosocial stressors in an adolescent:A case report

BACKGROUND Benign recurrent intrahepatic cholestasis(BRIC)is a rare autosomal recessive disorder,characterized by episodes of intense pruritus,elevated serum levels of alkaline phosphatase and bilirubin,and near-normal-glutamyl transferase.These episodes may persist for weeks to months before spontaneously resolving,with patients typically remaining asymptomatic between occurrences.Diagnosis entails the evaluation of clinical symptoms and targeted genetic testing.Although BRIC is recognized as a benign genetic disorder,the triggers,particularly psychosocial factors,remain poorly understood.CASE SUMMARY An 18-year-old Chinese man presented with recurrent jaundice and pruritus after a cold,which was exacerbated by self-medication involving vitamin B and paracetamol.Clinical and laboratory evaluations revealed elevated levels of bilirubin and liver enzymes,in the absence of viral or autoimmune liver disease.Imaging excluded biliary and pancreatic abnormalities,and liver biopsy demonstrated centrilobular cholestasis,culminating in a BRIC diagnosis confirmed by the identification of a novel ATP8B1 gene mutation.Psychological assessment of the patient unveiled stress attributable to academic and familial pressures,regarded as potential triggers for BRIC.Initial relief was observed with ursodeoxycholic acid and cetirizine,followed by an adjustment of the treatment regimen in response to elevated liver enzymes.The patient's condition significantly improved following a stress-related episode,thanks to a comprehensive management approach that included psychosocial support and medical treatment.CONCLUSION Our research highlights genetic and psychosocial influences on BRIC,emphasizing integrated diagnostic and management strategies.

Monogenic diabetes in children:An underdiagnosed and poorly managed clinical dilemma

Monogenic diabetes,constituting 1%-2%of global diabetes cases,arises from single gene defects with distinctive inheritance patterns.Despite over 50 associated genetic disorders,accurate diagnoses and management of monogenic diabetes remain inadequate,underscoring insufficient clinician awareness.The disease spectrum encompasses maturity-onset diabetes of the young(MODY),characterized by distinct genetic mutations affecting insulin secretion,and neonatal diabetes mellitus(NDM)-a heterogeneous group of severe hyperglycemic disorders in infants.Mitochondrial diabetes,autoimmune monogenic diabetes,genetic insulin resistance and lipodystrophy syndromes further diversify the monogenic diabetes landscape.A tailored approach based on phenotypic and biochemical factors to identify candidates for genetic screening is recommended for suspected cases of MODY.NDM diagnosis warrants immediate molecular genetic testing for infants under six months.Identifying these genetic defects presents a unique opportunity for precision medicine.Ongoing research aimed to develop cost-effective genetic testing methods and gene-based therapy can facilitate appropriate identification and optimize clinical outcomes.Identification and study of new genes offer a valuable opportunity to gain deeper insights into pancreatic cell biology and the pathogenic mechanisms underlying common forms of diabetes.The clinical review published in the recent issue of World Journal of Diabetes is such an attempt to fill-in our knowledge gap about this enigmatic disease.

Advancements in nutritional diagnosis and support strategies during the perioperative period for patients with liver cancer

Liver cancer represents a grave hepatic condition and constitutes a significant global health concern.Surgical resection remains the principal therapeutic modality for liver cancer.Nevertheless,perioperative malnutrition exerts a notable impact on patients with liver cancer,emerging as an independent risk factor for disease mortality and adverse outcomes.Hence,precise nutritional diagnosis and timely nutritional support hold the potential to enhance therapeutic efficacy and quality of life for liver cancer patients.This study represents a meticulous foray into the literature,extracting data from PubMed,Web of Science,and EMBASE databases,with a focus on the past 5 years.It scrutinizes the impact of malnutrition on patients undergoing liver cancer surgery,the etiological underpinnings of malnutrition within this patient cohort,the critical assessment of perioperative nutritional status,and the strategic approaches to nutritional support.Utilizing rigorous inclusion and exclusion criteria,the amassed scholarly works are meticulously synthesized,methodically organized,and categorically elaborated upon.Ultimately,the authors propose the incorporation of a multidisciplinary nutrition management team during the perioperative period,comprising nutritionists,pharmacists,physicians,nurses,psychologists,and rehabilitation therapists,among other specialized professionals.Together,they collaborate to devise and implement personalized nutritional support plans,monitor patients’nutritional status,and make necessary adjustments as required.Through comprehensive management and intervention,improvements in the nutritional status of liver cancer patients can be achieved,thereby enhancing surgical success rates and facilitating postoperative recovery.It is believed that this manuscript will offer valuable insights to advance the nutritional management during the perioperative phase of liver cancer,aiding in ameliorating patients'nutritional status and treatment outcomes.

The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.

Genetic variation and selection of introduced provenances of Siberian Pine(Pinus sibirica) in frigid regions of the Greater Xing'an Range,Northeast China

Siberian Pine （Pinus sibirica） is an ecologically and eco-nomically important species in pristine forests throughout northern Rus-sia. Four provenances of P. sibirica were introduced from Mongolia and Russia to the Greater Xing’an Range （the Daxing’anling）, northeast China in 1993. The aim of this research was to study genetic variation and selection of the introduced four Pinus sibirica provenances. Heights （H）, basal diameters （BD）, survival rates （SR） and crown lengths （CL） of different families were measured as primary outcomes in different growth years. Results of data analyses demonstrated high coefficients of phenotypic variation （PCV） and heritability （H2） for H, BD and CL at 18 years after introduction. PCV and H2 increased with age. Correlations of＆amp;nbsp;growth traits between any two growth years were all significantly positive, but the correlation coefficient was smaller when the growth year interval was larger. Correlations between H and the original environment factors decreased gradually, indicating that with long-term subsistence in the new environment, the influence of the source environment declined. Colligation of multiple traits to estimate provenances showed that Novosibirsk, Tomsk, and Altai Mountains had higher survival rates and biomass, and proved more suitable for introduction and plantation in the Greater Xing’an Range in China.

Current scenario of the genetic testing for rare neurological disorders exploiting next generation sequencing

Next generation sequencing is currently a cornerstone of genetic testing in routine diagnostics,allowing for the detection of sequence variants with so far unprecedented large scale,mainly in genetically heterogenous diseases,such as neurological disorders.It is a fast-moving field,where new wet enrichment protocols and bioinformatics tools are constantly being developed to overcome initial limitations.Despite the as yet undiscussed advantages,however,there are still some challenges in data analysis and the interpretation of variants.In this review,we address the current state of next generation sequencing diagnostic testing for inherited human disorders,particularly giving an overview of the available high-throughput sequencing approaches;including targeted,whole-exome and whole-genome sequencing;and discussing the main critical aspects of the bioinformatic process,from raw data analysis to molecular diagnosis.

Clinicopathological analysis of early-stage breast cancer patients that meet indications for BRCA 1/2 genetic testing

Objective:To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2(BRCA1/2)genetic testing in China.Methods:Based on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network(NCCN)clinical practice guidelines in oncology,genetic/familial high-risk assessment:Breast and ovarian(Version 2.2019),a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center,Peking University First Hospital between January 2008 and December 2016.Clinicopathological characteristics of all patients were analyzed,and prognoses were calculated using the KaplanMeier method and a Cox proportionate hazards model.Results:A total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group,accounting for34.7%of all breast cancer patients treated in Breast Disease Center,Peking University First Hospital during the study period.Compared with breast cancer patients without indications for BRCA genetic testing,the overall survival(OS)and disease-free survival(DFS)of patients with indications were not significantly different.In the study group,patients with premenopausal status,high T stage,lymph node positive,estrogen receptor(ER)negative,Ki-67>20%and presence of a vascular tumor thrombus had worse prognosis.There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications.Conclusions:Single-center data showed that more than 30%of patients with early-stage breast cancer had indications for BRCA genetic testing.There was no prognostic difference in patients with or without indications for BRCA genetic testing.Premenopausal status,high T stage,lymph node positive,ER negative,Ki-67>20%,and presence of a vascular tumor thrombus were associated with poor prognosis.

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.

Genetic association of urokinase-type plasminogen activator gene rs2227564 site polymorphism with sporadic Alzheimer's disease in the Han Chinese population

A missense C/T polymorphism in exon 6 （the NCBI rslD is rs2227564） of the urokinase-type plasminogen activator gene has been identified as a possible hot spot for Alzheimer＇s disease risk. The present study analyzed urokinase-type plasminogen gene polymorphisms of rs2227564 with sporadic Alzheimer＇s disease by PCR-restriction fragment length polymorphism. Results showed that CC, CT and TT genotype distribution frequencies had significant differences between sporadic Aizheimer＇s disease patients and healthy controls, in-depth analysis of the association between urokinase-type plasminogen gene rs2227564 polymorphisms and sporadic Alzheimer＇s disease indicated that people with the C-positive genotype CC ＋ CT were at a higher risk for developing sporadic Alzheimer＇s disease. These results support the contribution of the polymorphisms of rs2227564 in the urokinase-type plasminogen gene to the pathogenesis of sporadicAIzheimer＇s disease in the Han Chinese population.

Factors Affecting the Genetic Diagnostic Rate in Congenital Heart Disease

Background: Over 400 genes contribute to the development of congenital heart disease (CHD). Additionally,multisystemic manifestations accompanying syndromic CHD pose a higher risk of genetic diseases. This studyinvestigated the diagnostic yield of whole-exome sequencing (WES) in patients with sporadic syndromic CHDand the phenotypic factors affecting the genetic diagnostic rate. Methods: Sixty-four patients with sporadic syndromicCHD aged <18 years underwent WES between May 2018 and December 2020 in a single tertiary center,and the association between genetic testing data and extracardiac phenotypes was analyzed. Results: Extracardiacphenotypes were measured as 3.66 ± 3.05 (standard deviation, interquartile range: 2–5) items per patient. WESdetected diagnostic variants in 19 (29.7%) patients: seven (36.8%), seven (36.8%), and five (26.3%) with pathogenicvariants, likely pathogenic variants, and variants of unknown significance, respectively. Post-diagnosis surveillanceidentified the extracardiac phenotype in 54.5% (6/11) of patients. De novo variants accounted for 76.2%(15/19) of variants and autosomal dominant inheritance for 94.7% (18/19). Most diseases were ultra-rare. No significantdifferences were noted in cardiac and extracardiac phenotypes, single or combined (all P > 0.05), betweenthe groups with and without a diagnostic variant. However, patients with ≥3 extracardiac phenotypes had a significantlyhigher likelihood of having a diagnostic variant than those with ≤2 (38.3% vs. 5.9%, odds ratio = 9.93,95% confidence interval = 1.21–81.44, P = 0.013). Conclusions: The number of extracardiac phenotypes is importantin predicting the possibility of genetic diagnosis. Physicians will be able to select patients with a high probabilityof genetic diagnosis and provide appropriate genetic counseling based on the results of this study.

2+0 CYP21A2 deletion carrier—a limitation of the genetic testing and counseling:A case report

BACKGROUND CYP21A2 gene mutations may all cause reduction or loss of 21-hydroxylase activity,leading to development of congenital adrenal hyperplasia(CAH)with different clinical phenotypes.For families with CAH children,genetic testing of the parents and genetic counseling are recommended to assess the risk of recurrence.CASE SUMMARY We report a case of CAH with a high suspicion before delivery.The risk of the child suffering from CAH during the pregnancy had been underestimated due to the deviation of genetic counseling and genetic testing results.Our report confirmed a CYP21A2 homozygous deletion in this case,CYP21A2 heterozygous deletion in the mother,and a rare 2+0 CYP21A2 deletion in the father.CONCLUSION It is important to analyze the distribution of CYP21A2 gene in the two alleles of parents of children with CAH.

Whole-genome amplification/preimplantation genetic testing for propionic acidemia of successful pregnancy in an obligate carrier Mexican couple:A case report

BACKGROUND Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple genetic disorders at once.Here,we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects(PGT-M)approach for detecting propionic acidemia(PA)in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit(PCCA)couple.CASE SUMMARY A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic counseling.They were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit(PCCB)genotype.Next-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant(c.2041-1G>T,ClinVar:RCV-000802701.1;dbSNP:rs1367867218)in both parents.The couple requested in vitro fertilization(IVF)and PGT-M for PA.From IVF,12 oocytes were collected and fertilized,of which two resulted in high-quality embryos.Trophectoderm biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were euploid.Endpoint polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type PCCA male embryo and a heterozygous c.2041-1G>T female embryo.Both embryos were transferred,resulting in a clinical pregnancy and the delivery of a healthy male newborn(38 wk,weight:4080 g,length:49 cm,APGAR 9/9).The absence of PA was confirmed by expanded newborn screening.CONCLUSION We show that using PGT-M with Whole Genome Amplification templates,coupled with IVF,can reduce the transmission of a pathogenic variant of the PCCA gene.

Role of genetic testing in cardiomyopathies:Αprimer for cardiologists

Recent advances in cardiovascular genetics have transformed genetic testing into a valuable part of management of families with inherited cardiomyopathies.As novel mutations have been identified,understanding when to consider genetic testing has emerged as an important consideration in the management of these cases.Specific genetic testing has a paramount importance in the risk stratification of family members,in the prognosis of probands at higher risk of a serious phenotype expression,and finally in the identification of new mutations,all of which are discussed in this review.The indications for each type of cardiomyopathy are described,along with the limitations of genetic testing.Finally,the importance of public sharing of variants in large data sets is emphasized.The ultimate aim of this review is to present key messages about the genetic testing process in order to minimize potential harms and provide suggestions to specialized clinicians who act as a part of a multidisciplinary team in order to offer the best care to families with inherited cardiomyopathies.

Uncertainty following an inconclusive result from the BRCA1/2 genetic test:A review about psychological outcomes

BACKGROUND An inconclusive result from BRCA1/2 genetic testing indicates that a genetic variant of uncertain significance is detected.This case constitutes the majority of genetic test results,but studies specifically addressing the psychological adjustment of people with inconclusive results are scarce.AIM To examine psychological outcomes of receiving an uninformative BRCA1/2 test result.METHODS PubMed,PsychInfo,and Cochrane Central Register of Controlled Trials were screened for studies focusing on distress,anxiety,and depression levels in individuals with inconclusive genetic test results.This review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method.RESULTS Studies on psychological outcomes of inconclusive BRCA1/2 focused on general and specific distress,anxiety,and depression.Overall,they produced mixed results.These inconsistent findings are probably due to the uncertainty caused by this type of result,that may also influence the decisions of individuals about surveillance and prophylactic options,reducing their compliance.In addition,this review highlights specific risk and protective factors that affect psychological adjustment in individuals with an inconclusive genetic testing result.CONCLUSION Individuals with inconclusive genetic test results need specific educational programs and support to better understand the meaning of their results in order to be able to make decisions about surveillance and prophylactic options.

Endoscopic ultrasound-guided fine-needle aspiration pancreatic adenocarcinoma samples yield adequate DNA for next-generation sequencing:A cohort analysis

BACKGROUND Genetic tests are increasingly performed for the management of unresectable pancreatic cancer.For genotyping aimed samples current guidelines recommend using core specimens,although based on moderate quality evidence.However,in clinical practice among the endoscopic ultrasound(EUS) guided tissue acquisition methods,fine needle aspiration(FNA) is the most widely performed.AIM To assess the adequacy for next generation sequencing(NGS) of the DNA yielded from EUS-FNA pancreatic adenocarcinoma(PDAC) samples.METHODS Between November 2018 and December 2021,105 patients with PDAC confirmed by EUS-FNA were included in the study at our tertiary gastroenterology center.Either 22 gauge(G) or 19G FNA needles were used.One pass was dedicated to DNA extraction.DNA concentration and purity(A260/280,A260/230) were assessed by spectrophotometry.We assessed the differences in DNA parameters according to needle size and tumor characteristics(size,location) and the adequacy of the extracted DNA for NGS(defined as A260/280 ≥ 1.7,and DNA yield:≥ 10 ng for amplicon based NGS,≥ 50 ng for whole exome sequencing [WES],≥ 100 ng for whole genome sequencing [WGS]) by analysis of variance and ttest respectively.Moreover,we compared DNA purity parameters across the different DNA yield categories.RESULTS Our cohort included 49% male patients,aged 67.02 ± 8.38 years.The 22G needle was used in 71%of the cases.The DNA parameters across our samples varied as follows:DNA yield:1289 ng(inter quartile range:534.75-3101),A260/280 = 1.85(1.79-1.86),A260/230 = 2.2(1.72-2.36).DNA yield was > 10 ng in all samples and > 100 ng in 93% of them(one sample < 50 ng).There were no significant differences in the concentration and A260/280 between samples by needle size.Needle size was the only independent predictor of A260/230 which was higher in the 22G samples(P =0.038).NGS adequacy rate was 90% for 19G samples regardless of NGS type,and for 22G samples it reached 89% for WGS adequacy and 91% for WES and amplicon based NGS.Samples with DNA yield > 100 ng had significantly higher A260/280(1.89 ± 0.32 vs 1.34 ± 0.42,P = 0.013).Tumor characteristics were not corelated with the DNA parameters.CONCLUSION EUS-FNA PDAC samples yield DNA adequate for subsequent NGS.DNA amount was similar between 22G and 19G FNA needles.DNA purity parameters may vary indirectly with needle size.

Rare adult neuronal ceroid lipofuscinosis associated with CLN6 gene mutations:A case report

BACKGROUND Adult neuronal ceroid lipofuscinosis(ANCL)can be caused by compound heterozygous recessive mutations in CLN6.The main clinical features of the disease are neurodegeneration,progressive motor dysfunction,seizures,cognitive decline,ataxia,vision loss and premature death.CASE SUMMARY A 37-year-old female presented to our clinic with a 3-year history of limb weakness and gradually experiencing unstable walking.The patient was diagnosed with CLN6 type ANCL after the identification of mutations in the CLN6 gene.The patient was treated with antiepileptic drugs.The patient is under ongoing followup.Unfortunately,the patient’s condition has deteriorated,and she is currently unable to care for herself.CONCLUSION There is presently no effective treatment for ANCL.However,early diagnosis and symptomatic treatment are possible.

Novel mutation of SPG4 gene in a Chinese family with hereditary spastic paraplegia:A case report

BACKGROUND Hereditary spastic paraplegia(HSP)is a group of neurogenetic diseases of the corticospinal tract,accompanied by distinct spasticity and weakness of the lower extremities.Mutations in the spastic paraplegia type 4(SPG4)gene,encoding the spastin protein,are the major cause of the disease.This study reported a Chinese family with HSP caused by a novel mutation of the SPG4 gene.CASE SUMMARY A 44-year-old male was admitted to our hospital for long-term right lower limb weakness,leg stiffness,and unstable walking.His symptoms gradually worsened,while no obvious muscle atrophy in the lower limbs was found.Neurological examinations revealed that the muscle strength of the lower limbs was normal,and knee reflex hyperreflexia and bilateral positive Babinski signs were detected.Members of his family also had the same symptoms.Using mutation analysis,a novel heterozygous duplication mutation,c.1053dupA,p.(Gln352Thrfs*15),was identified in the SPG4 gene in this family.CONCLUSION A Chinese family with HSP had a novel mutation of the SPG4 gene,which is autosomal dominant and inherited as pure HSP.The age of onset,sex distribution,and clinical manifestations of all existing living patients in this family were analyzed.The findings may extend the current knowledge on the existing mutations in the SPG4 gene.