Tay-Sachs Research Articles

Storage of GM2 ganglioside and altered gene expression in infantile Tay-Sachs disease during fetal development has implications for therapeutic timing and efficacy

Storage of GM2 ganglioside and altered gene expression in infantile Tay-Sachs disease during fetal development has implications for therapeutic timing and efficacy

Lysosomal gene Hexb displays haploinsufficiency in a knock-in mouse model of Alzheimer’s disease

Lysosomal network abnormalities are an increasingly recognised feature of Alzheimer’s disease (AD), which appear early and are progressive in nature. Sandhoff disease and Tay-Sachs disease (neurological lysosomal storage diseases caused by mutations in genes that code for critical subunits of β-hexosaminidase) result in accumulation of amyloid-β (Aβ) and related proteolytic fragments in the brain. However, experiments that determine whether mutations in genes that code for β-hexosaminidase are risk factors for AD are currently lacking. To determine the relationship between β-hexosaminidase and AD, we investigated whether a heterozygous deletion of Hexb, the gene that encodes the beta subunit of β-hexosaminidase, modifies the behavioural phenotype and appearance of disease lesions in AppNL-G-F/NL-G-F(AppKI/KI) mice. AppKI/KI and Hexb+/- mice were crossed and evaluated in a behavioural test battery. Neuropathological hallmarks of AD and ganglioside levels in the brain were also examined. Heterozygosity of Hexb in AppKI/KI mice reduced learning flexibility during the Reversal Phase of the Morris water maze. Contrary to expectation, heterozygosity of Hexb caused a small but significant decrease in amyloid beta deposition and an increase in the microglial marker IBA1 that was region- and age-specific. Hexb heterozygosity caused detectable changes in the brain and in the behaviour of an AD model mouse, consistent with previous reports that described a biochemical relationship between HEXB and AD. This study reveals that the lysosomal enzyme gene Hexb is not haplosufficient in the mouse AD brain.

COMPOUND HETEROZYGOTE REASON FOR JUVENILE FORM OF TAY-SACHIS DISEASE -CASE REPORT

Tay-Sachs diseases are group of rare autosomal recessive lysosomal disorders, GM2-gangliozidoses. They are progressive neurodegenerative diseases, caused by a mutation in the enzyme β-hexosaminidase A. Depending on the time of presentation of symptoms, there are three forms: infantile, juvenile and adult. We present a 8 year old patient, who is presented at the age of 4 with progressive deterioration in psychomotor and speech skills, pyramidal symptoms, ataxia and muscle weakness. The EEG showed bihemispheric fast spike waves and the MRI showed no findings of organic disease. Finally a molecular genetic testing was made, which proved the diagnosis of juvenile form of Tay-Sachs disease. It was determined that the patient is a compound heterozygote, with two different mutations in the alleles of the HEXA gene, one  inherited from the mother and the other one from the father. The juvenile Tay-Sachs disease is characterized with beginnig between the age of 2 to 10 years old. Clinically it is presented with muscle weakness, incoordination, ataxia, dysarthria, dysphagia and progressive spasticity. It progresses to development of dementia, convulsions, blindness and vegetative state with decerebrate rigidity and death by the age of 15. It is inherited autosomal recessive with one mutation present on both alleles of the HEXA gene. Treatment options for Tay-Sachs disease currently are only symptomatic and supportive. There are ongoing researches for curative treatments for Tay-Sachs, like enzyme replacement, chaperone, substrate reduction and gene therapy. Keywords: Tay-Sachs disease, juvenile form, compound heterozygote.  

Neurodegeneration with Progressive Dystonia: Juvenile-Onset Tay-Sachs Disease.

Neurodegeneration with Progressive Dystonia: Juvenile-Onset Tay-Sachs Disease.

Increased phosphorylation of HexM improves lysosomal uptake and potential for managing GM2 gangliosidoses

Tay-Sachs and Sandhoff diseases are genetic disorders resulting from mutations in HEXA or HEXB, which code for the α- and β-subunits of the heterodimer β-hexosaminidase A (HexA), respectively. Loss of HexA activity results in the accumulation of GM2 ganglioside (GM2) in neuronal lysosomes, culminating in neurodegeneration and death, often by age 4. Previously, we combined critical features of the α- and β-subunits of HexA into a single subunit to create a homodimeric enzyme known as HexM. HexM is twice as active as HexA and degrades GM2 in vivo, making it a candidate for enzyme replacement therapy (ERT). Here we show HexM production is scalable to meet ERT requirements and we describe an approach that enhances its cellular uptake via co-expression with an engineered GlcNAc-1-phosphotransferase that highly phosphorylates lysosomal proteins. Further, we developed a HexA overexpression system and functionally compared the recombinant enzyme to HexM, revealing the kinetic differences between the enzymes. This study further advances HexM as an ERT candidate and provides a convenient system to produce HexA for comparative studies.

Article on Tay-Sachs Disease

Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord..also known as GM2 gangliosidosis or Hexosaminidase A deficiency) is an autosomal recessive genetic disorder. In its most common variant known as infantile Tay-Sachs disease it presents with a relentless deterioration of mental and physical abilities which commences at 6 months of age and usually results in death by the age of four.It is caused by a genetic defect in a single gene with one defective copy of that gene inherited from each parent. The disease occurs when harmful quantities of gangliosides accumulate in the nerve cells of the brain, eventually leading to the premature death of those cells. There is currently no cure or treatment. Tay- Sachs disease is a rare disease. Other autosomal disorders such as cystic fibrosis and sickle cell anemia are far more common. TSD is an autosomal recessive genetic disorder, meaning that when both parents are carriers, there is a 25% risk of giving birth to an affected child.

Carrier Screening for Single-Gene Disorders – A Brief Review

Summary Carrier screening (CS) is an approach to pre-reproductive identification of couples at risk of having offspring with a single-gene disorder (SGD). The goal of CS is to facilitate reproductive autonomy and informed decision-making of the revealed risk couples. Initially, CS was introduced in the 1970s among the Ashkenazi Jewish population in the USA with a high incidence of Tay-Sachs disease. Until recently, CS had a limited application, mainly among individuals of a particular ethnicity or family history of SGD, and a limited number of conditions are included. Implementing the revolutionary technology of next-generation sequencing revealed a much more comprehensive range of possibilities for CS. The expanded alternative variant introduced a new concept that allows screening for hundreds to thousands of SGDs without pre-selection of individuals based on their ancestry or family history. Furthermore, the number of detected pathogenic variants is much higher compared to the traditional CS. Currently, there is insufficient experience with the application of expanded CS, and the lack of uniform guidelines is a major problem when it comes to massive implementation. Nevertheless, the significant potential of the expanded CS has given rise to a growing interest in it and provoked in-depth discussions about the opportunities of widespread application in practice.

Pontocerebellar atrophy is the hallmark neuroradiological finding in late-onset Tay-Sachs disease.

Late-onset Tay-Sachs disease (LOTS) is a form of GM2 gangliosidosis, an autosomal recessive neurodegenerative disorder characterized by slowly progressive cerebellar ataxia, lower motor neuron disease, and psychiatric impairment due to mutations in the HEXA gene. The aim of our work was to identify the characteristic brain MRI findings in this presumably underdiagnosed disease. Clinical data and MRI findings from 16 patients (10F/6M) with LOTS from two centers were independently assessed by two readers and compared to 16 age- and sex-related controls. Lower motor neuron disease (94%), psychiatric symptoms-psychosis (31%), cognitive impairment (38%) and depression (25%)-and symptoms of cerebellar impairment including dysarthria (94%), ataxia (81%) and tremor (69%), were the most common clinical features. On MRI, pontocerebellar atrophy was a constant finding. Compared to controls, LOTS patients had smaller mean middle cerebellar peduncle diameter (p < 0.0001), mean superior cerebellar peduncle diameter (p = 0.0002), mesencephalon sagittal area (p = 0.0002), pons sagittal area (p < 0.0001), and larger 4th ventricle transversal diameter (p < 0.0001). Mild corpus callosum thinning (37.5%), mild cortical atrophy (18.8%), and white matter T2 hyperintensities (12.5%) were also present. Given the characteristic clinical course and MRI findings of the pontocerebellar atrophy, late-onset Tay-Sachs disease should be considered in the differential diagnosis of adult-onset cerebellar ataxias.

L-Arginine Ameliorates Defective Autophagy in GM2 Gangliosidoses by mTOR Modulation.

Aims: Tay–Sachs and Sandhoff diseases (GM2 gangliosidosis) are autosomal recessive disorders of lysosomal function that cause progressive neurodegeneration in infants and young children. Impaired hydrolysis catalysed by β-hexosaminidase A (HexA) leads to the accumulation of GM2 ganglioside in neuronal lysosomes. Despite the storage phenotype, the role of autophagy and its regulation by mTOR has yet to be explored in the neuropathogenesis. Accordingly, we investigated the effects on autophagy and lysosomal integrity using skin fibroblasts obtained from patients with Tay–Sachs and Sandhoff diseases. Results: Pathological autophagosomes with impaired autophagic flux, an abnormality confirmed by electron microscopy and biochemical studies revealing the accelerated release of mature cathepsins and HexA into the cytosol, indicating increased lysosomal permeability. GM2 fibroblasts showed diminished mTOR signalling with reduced basal mTOR activity. Accordingly, provision of a positive nutrient signal by L-arginine supplementation partially restored mTOR activity and ameliorated the cytopathological abnormalities. Innovation: Our data provide a novel molecular mechanism underlying GM2 gangliosidosis. Impaired autophagy caused by insufficient lysosomal function might represent a new therapeutic target for these diseases. Conclusions: We contend that the expression of autophagy/lysosome/mTOR-associated molecules may prove useful peripheral biomarkers for facile monitoring of treatment of GM2 gangliosidosis and neurodegenerative disorders that affect the lysosomal function and disrupt autophagy.

Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

Globally, about 6% of children are born with a serious birth defect of genetic or partially genetic origin. Carrier screening or testing is one way to identify couples at increased risk of having a child with an autosomal recessive condition. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in high-risk populations of specific ancestral backgrounds. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if testing is only offered in an antenatal setting. This is an update of a previously published review. To assess the effectiveness of systematic preconception genetic risk assessment to enable autonomous reproductive choice and to improve reproductive outcomes in women and their partners who are both identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. Date of latest search of the registers: 04 August 2021. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials. Date of latest search of all these sources: 25 June 2021. SELECTION CRITERIA: Any randomised controlled trials (RCTs) or quasi-RCTs (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care. We identified 37 papers, describing 22 unique trials which were potentially eligible for inclusion in the review. However, after assessment, we found no RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease. No RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease are included. A trial identified earlier has published its results and has subsequently beenlisted as excluded in this review. As there are no RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease included in either the earlier or current versions of this review, we recommend considering potential non-RCTs studies (for example prospective cohorts or before-and-after studies) for future reviews. While RCTs are desirable to inform evidence-based practice and robust recommendations, the ethical, legal and social implications associated with using this trial design to evaluate the implementation of preconception genetic risk assessment involving carrier testing and reproductive autonomy must also be considered. In addition, rather than focusing on single gene-by-gene carrier testing for specific autosomal-recessive conditions as the intervention being evaluated, preconception expanded genetic screening should also be included in future searches as this has received much attention in recent years as a more pragmatic strategy. The research evidence for current international policy recommendations is limited to non-randomised studies.

Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG)

Carrier screening began 50 years ago with screening for conditions that have a high prevalence in defined racial/ethnic groups (e.g., Tay–Sachs disease in the Ashkenazi Jewish population; sickle cell disease in Black individuals). Cystic fibrosis was the first medical condition for which panethnic screening was recommended, followed by spinal muscular atrophy. Next-generation sequencing allows low cost and high throughput identification of sequence variants across many genes simultaneously. Since the phrase “expanded carrier screening” is nonspecific, there is a need to define carrier screening processes in a way that will allow equitable opportunity for patients to learn their reproductive risks using next-generation sequencing technology. An improved understanding of this risk allows patients to make informed reproductive decisions. Reproductive decision making is the established metric for clinical utility of population-based carrier screening. Furthermore, standardization of the screening approach will facilitate testing consistency. This practice resource reviews the current status of carrier screening, provides answers to some of the emerging questions, and recommends a consistent and equitable approach for offering carrier screening to all individuals during pregnancy or preconception.

GM2 gangliosidoses: evaluation of clinical, biochemical and genetic findings of patients with three novel mutations

Purpose: The aim of this study is to evaluate the diagnosis characteristics, clinic findings, phenotypical and genotypical features of children with GM2 gangliosidoses.&#x0D; Materials and Methods: The file records of 14 patients diagnosed with GM2 gangliosidoses in our clinic were retrospectively reviewed. The GM2 gangliosidoses diagnosis was confirmed by determining the levels of serum total hexosaminidase and β-hexosaminidase activity with genetic analysis. &#x0D; Results: We identified a total of seven different mutations, three of which were novel (one in the HEXA gene and two in the HEXB gene) in 14 patients. We found a high frequency of c.1100_1111del (p.Gly367_Tyr370del) mutation in HEXA affected patients. The mean age at diagnosis was 13.46.3 months and 14.24.2 months for patients with Tay–Sachs disease (TSD) and Sandhoff disease (SD) respectively. Neuroregression was present in 92.9% of our patients. Of the 14 patients, 11 had epilepsy, 10 had developmental delay, 6 had hyperacusis, 6 had cherry-red spots and 6 had macrocephaly, but none of the patients had organomegaly. &#x0D; Conclusion: GM2 gangliosidoses disease should be considered for children with developmental regression and/or delay. For early diagnosis, enzyme analysis and gene detection should be performed in children with suspected GM2 gangliosidoses in the presence of clinical findings.

Analysis of the HEXA, HEXB, ARSA, and SMPD1 Genes in 68 Iranian Patients.

Lysosomal storage diseases (LSDs) are known as genetic disorders with an overall prevalence of 1 per 7700 live births. Sphingolipidosis, which is a subgroup of LSDs, is resulted from mutations in the coding genes of specific enzymes of sphingolipid hydrolases. The current study aimed to provide additional knowledge on the genotype of sphingolipidoses disease among Iranian patients affected by the disease. In this research, we studied 68 unrelated Iranian patients diagnosed with one kind of sphingolipidoses from 2014 to 2019. Thereafter, genomic DNA was isolated from their peripheral blood leukocytes samples in EDTA in terms of the manufacturer's protocol. All the coding exons and exon-intron boundaries of the related genes were sequenced and then analyzed using the NCBI database. Finally, they were reviewed using some databases such as the Human Gene Mutation Database (HGMD) and ClinVar ( https://www.ncbi.nlm.nih.gov/clinva ). By studying 22 MLD patients, 18 different variations of the ARSA gene were found, one of which was new including, named as c.472T > G p. (Cys158Gly). Out of 15 Sandhoff disease (SD) patients, 11 different variations of the HEXB gene were found. Correspondingly, the c.1083-2delA was not reported earlier. By investigating 21 Iranian patients with Tay-Sachs disease (TSD), one new variant was found as c.622delG. The study of 10 Niemann-Pick disease A/B (NPDA/B (patients has led to the identification of 9 different SMPD1 gene variations, among which 3 variations were novel mutations. The results of the present study can be expanded to the genotypic spectrum of Iranian patients with MLD, SD, TSD, and NPD diseases and also used to innovate more effective methods for the detection of genetic carriers as well as diagnosing and counseling of Iranian patients affected with these disorders.

Natural history of Tay-Sachs disease in sheep

Tay-Sachs disease (TSD) is a fatal neurodegenerative disease caused by a deficiency of the enzyme β-N-acetylhexosaminidase A (HexA). TSD naturally occurs in Jacob sheep is the only experimental model of TSD. TSD in sheep recapitulates neurologic features similar to juvenile onset and late onset TSD patients. Due to the paucity of human literature on pathology of TSD, a better natural history in the sheep TSD brain, which is on the same order of magnitude as a child's, is necessary for evaluating therapy and characterizing the pathological events that occur. To provide clinicians and researchers with a clearer understanding of longitudinal pathology in patients, we compare spectrum of clinical signs and brain pathology in mildly symptomatic (3-months), moderately symptomatic (6-months), or severely affected TSD sheep (humane endpoint at ~9-months of age). Increased GM2 ganglioside in the CSF of TSD sheep and a TSD specific biomarker on MRS (taurine) correlate with disease severity. Microglial activation and reactive astrocytes were observed globally on histopathology in TSD sheep with a widespread reduction in oligodendrocyte density. Myelination is reduced primarily in the forebrain illustrated by loss of white matter on MRI. GM2 and GM3 ganglioside were increased and distributed differently in various tissues. The study of TSD in the sheep model provides a natural history to shed light on the pathophysiology of TSD, which is of utmost importance due to novel therapeutics being assessed in human patients.

Microglia-Specific Expression of HEXA and HEXB Leads to Poor Prognosis in Glioblastoma Patients

Glioblastoma multiforme (GBM) is one of the deadliest cancers in brain. There have been few treatment advances for GBM despite increasing scientific understanding of this disease. β-hexosaminidase (Hex) is an important enzyme system in human body, encoded by two genes, HEXA and HEXB, are closely related to central nervous system (CNS) diseases such as Sandhoff disease (SD) and Tay-Sachs disease (TSD). However, the expression pattern and function of HEXA and HEXB in GBM remains unclear. Here, we found that both the mRNA and protein expression levels of HEXA and HEXB were significantly upregulated in GBM patient samples. The results from single-cell RNA-sequencing (scRNA-seq) database and double immunostaining showed that HEXA and HEXB were specifically expressed in microglia in GBM patient samples. Furthermore, our in vitro experiments revealed that conditioned media from HEXA and HEXB knockdown-microglia cells could inhibit the proliferation and migration of GBM cells. Finally, according to survival analysis based on online database, higher expression of HEXA and HEXB was associated with poor prognosis in GBM patients. In conclusion, these results suggest that microglial HEXA and HEXB play fundamental role in GBM progression, and they will be potential biomarkers for GBM.

Tay – Sachs Disease

Tay-Sachs disease is a rare hereditary disease that increasingly destroys nerve cells (neurons) in the brain and nerve structure. The foremost common variety of monogenic disorder becomes apparent in infancy. Babies with this disease usually look traditional till the age of three to six months, once their development slows and muscles used for movement weaken. Affected infants lose motor skills like turning over, sitting, and travel. They additionally develop Associate in nursing exaggerated start to loud noises. Because the sickness progresses, youngsters with monogenic disorder expertise seizures, vision and deafness, intellectual incapacity, and disfunction. Youngsters with this severe infantile variety of monogenic disorder sometimes live solely into infancy.

The Insight in Modern Genetic Engineering Application

Introduction: Genetic engineering is a wide array of techniques that alter the genetic constitution of cells or individuals by selective removal, insertion, or modification of individual genes. Methods: This research work includes technology that covered the advanced space from gene cloning to the cure of the disease. Genetic engineering and the human section acknowledge the Crick and Watson research on double-strand DNA. Disease and prevention highlight how genetic engineering has advanced in disease screening and the development of treatment through gene modification. The prospective advancement and achievement from the past to now in the genetic field are shown in this research paper. Results: The Insight in modern Genetic Engineering Application acknowledges the reader’s motive to know the basic principle of genetic engineering in health specialization. Since the development of double helices DNA, the research in genetics has taken rapid speed in the development of advanced modality in its benefits. Genetic engineering application in genetic disease disorder assists in the identification and its importance in the remedy of the disorder. The advanced paper helps to understand how gene therapy helps to understand genetic disorders like Down syndrome, Huntington's disease, sickle-cell anemia, and Tay-Sachs disease and its solution through gene splicing and modification. In general, the enhancement in modern bioengineering in genetics shows the way to generate economic benefits which include improved plants and animals for agriculture, and efficient production of valuable biopharmaceuticals. Conclusion: The genetic engineering application study was done for the briefs evaluation of development in genetic engineering from its application to disease screening to treatment.

Magnetic resonance imaging and spectroscopy in late-onset GM2-gangliosidosis

ObjectiveOur study aimed to quantify structural changes in relation to metabolic abnormalities in the cerebellum, thalamus, and parietal cortex of patients with late-onset GM2-gangliosidosis (LOGG), which encompasses late-onset Tay-Sachs disease (LOTS) and Sandhoff disease (LOSD). MethodsWe enrolled 10 patients with LOGG (7 LOTS, 3 LOSD) who underwent a neurological assessment battery and 7 age-matched controls. Structural MRI and MRS were performed on a 3 T scanner. Structural volumes were obtained from FreeSurfer and normalized by total intracranial volume. Quantified metabolites included N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), and combined glutamate-glutamine (Glx). Metabolic concentrations were corrected for partial volume effects. ResultsStructural analyses revealed significant cerebellar atrophy in the LOGG cohort, which was primarily driven by LOTS patients. NAA was lower and mI higher in LOGG, but this was also significantly driven by the LOTS patients. Clinical ataxia deficits (via the Scale for the Assessment and Rating of Ataxia) were associated with neuronal injury (via NAA), neuroinflammation (via mI), and volumetric atrophy in the cerebellum. InterpretationThe decrease of NAA in the cerebellum suggests that, in addition to cerebellar atrophy, there is ongoing impaired neuronal function and/or loss, while an increase in mI indicates possible neuroinflammation in LOGG (more so within the LOTS subvariant). Quantifying cerebellar atrophy in relation to neurometabolic differences in LOGG may lead to improvements in assessing disease severity, progression, and pharmacological efficacy. Lastly, additional neuroimaging studies in LOGG are required to contrast LOTS and LOSD more accurately.

Investigating Immune Responses to the scAAV9-HEXM Gene Therapy Treatment in Tay-Sachs Disease and Sandhoff Disease Mouse Models.

GM2 gangliosidosis disorders are a group of neurodegenerative diseases that result from a functional deficiency of the enzyme β-hexosaminidase A (HexA). HexA consists of an α- and β-subunit; a deficiency in either subunit results in Tay–Sachs Disease (TSD) or Sandhoff Disease (SD), respectively. Viral vector gene transfer is viewed as a potential method of treating these diseases. A recently constructed isoenzyme to HexA, called HexM, has the ability to effectively catabolize GM2 gangliosides in vivo. Previous gene transfer studies have revealed that the scAAV9-HEXM treatment can improve survival in the murine SD model. However, it is speculated that this treatment could elicit an immune response to the carrier capsid and “non-self”-expressed transgene. This study was designed to assess the immunocompetence of TSD and SD mice, and test the immune response to the scAAV9-HEXM gene transfer. HexM vector-treated mice developed a significant anti-HexM T cell response and antibody response. This study confirms that TSD and SD mouse models are immunocompetent, and that gene transfer expression can create an immune response in these mice. These mouse models could be utilized for investigating methods of mitigating immune responses to gene transfer-expressed “non-self” proteins, and potentially improve treatment efficacy.

Impact of Pan-Ethnic Expanded Carrier Screening in Improving Population Health Outcomes: Proceedings from a Multi-Stakeholder Virtual Roundtable Summit, June 25, 2020.

Impact of Pan-Ethnic Expanded Carrier Screening in Improving Population Health Outcomes: Proceedings from a Multi-Stakeholder Virtual Roundtable Summit, June 25, 2020.