Congenital hereditary endothelial dystrophy with progressive sensorineural deafness: a case report of Harboyan syndrome

ABSTRACT We present the case of a 37-year-old woman who underwent bilateral penetrating keratoplasty for congenital hereditary endothelial dystrophy at the age of 10 years. Over the subsequent 27 years, the patient's vision slowly deteriorated. Our examination revealed decompensation of the right corneal graft. We addressed this with regraft surgery. We then learned that the patient had been suffering from progressive hearing loss since adolescence. Tonal audiometry revealed hearing per ceptive deafness of 25 dB, which was more prominent in the left ear. Because the patterns of progressive sensorineural hearing loss and congenital hereditary endothelial dystrophy have both been linked to the same gene, slc4a11, we tested our patient for mutations in this gene. The test was positive for a heterozygous slc4a11 gene fifth exon mutation on chromosome 20p13-p12, which causes a frameshift. A combined clinical and genetic evaluation confirmed a diagnosis of Harboyan syndrome. After the genetic diagnosis of the disease, she was evaluated for the need for a hearing aid due to her hearing loss. The patient was also informed about genetic counseling.

Assessment of acute, subacute genetic toxicities and immunomodulatory activity of palm (Trachycarpus fortunei) buds.

ETHNOPHARMACOLOGY RELEVANCE: Palm buds are a natural green resource of the forest, which are not only rich in nutrients but contain a large number of phenolic acids and flavonoids, among other components. It has a variety of biological activities such as antioxidant and uterine smooth muscle stimulation. AIM OF THE STUDY: To evaluate the safety of palm buds for use as a nutraceutical product and food by evaluating the toxicity, subacute toxicity and genotoxicity of the young palm buds. Also studied for its immune-enhancing activity. MATERIALS AND METHODS: Acute toxicity tests were performed in mice using the maximum tolerance method, and the manifestations of toxicity and deaths were recorded after administration of 10,000 mg/mL for 14 consecutive d (days) of observations. To assess subacute toxicity, mice were treated with palm buds (750, 1500, or 3000 mg/mL) daily for 28 days. The teratogenicity of palm buds was assessed by the Ames test, the mouse bone marrow cell micronucleus test, and the mouse spermatozoa malformation test. In addition, we evaluated the immune-enhancing ability of palm buds by the mouse carbon profile test, delayed-type metamorphosis reaction, and serum hemolysin assay. RESULTS: In the acute toxicity study, the Median Lethal Dose (LD50) was greater than 10,000 mg/kg bw in both male and female rats. There were also no deaths or serious toxicities in the subacute study. The no-observed-adverse-effect level (NOAEL) was 3000 mg/kg bw. However, the mice's food intake decreased after one week. The medium and high dose groups had a reducing effect on body weight in mice of both sexes. In addition, the changes in organ coefficients of the liver, kidney and stomach in male mice were significantly higher in the high-dose group (3.23 ± 0.35, 0.75 ± 0.05, 0.57 ± 0.05 g) than in the control group (2.94 ± 0.18, 0.58 ± 0.05, 0.50 ± 0.02 g). Hematological analyses showed that all the indices of the rats in each palm sprout dose group were within the normal range. The results of blood biochemical indicators showed that there was a significant reduction in TP in the blood of male mice in the high-dose group (44.6 ± 7.8 g/L) compared to the control group (58.3 ± 15.1 g/L). In histopathological analysis, none of the significant histopathological changes were observed. The results of the immunological experiment in mice showed that the liver coefficient and thymus coefficient of the high-dose group (8400 mg/kg) were significantly lower than the control group. There was no remarkable difference in auricle swelling between each dose palm bud group (1400, 2800, or 8400 mg/kg) and the control group. The anti-volume number of the high-dose group was significantly increased. CONCLUSION: Palm buds have non-toxic effects in vivo and have little effect on non-specific and cellular immunity in the test mice within the dose range of this experiment. The immunoenhancement in mice is mainly achieved through humoral immunity. In conclusion, our results suggest that palm buds are safe for use as healthcare products and food.

The effect of genetic polymorphisms in STIM1 and ORAI1 on erythropoietin resistance in Egyptian patients with end-stage renal disease.

Chronic renal failure (CRF) is an incurable disease with unique challenges. Anemia is a frequent complication affecting dialysis patients. Erythropoietin (EPO) is used to treat anemia, but a poor response may result. We investigated genetic polymorphisms of store-operated calcium channel (SOC) signaling, an important erythropoietin-activated pathway that may induce EPO resistance in patients with renal failure. A total of 108 end stage renal disease (ESRD) patients were selected for this study. Patients were divided into two groups according to their erythropoietin resistance index (ERI): 39 patients with an ERI>10 and 69 patients with an ERI<10. We selected four tagging single nucleotide polymorphisms (tSNPs) in STIM1 and five in ORAI1 in our study. A polymerase chain reaction was performed, and genotyping against EPO resistance was correlated. Patients with the AG genotype of rs1561876 in STIM1, the TC genotype of rs6486795 in ORAI1, and the TG or GG genotypes of rs12320939 in ORAI1 were associated with an increased risk of erythropoietin resistance. Overall, we reported a moderately significant relationship between genetic polymorphisms of STIM1 and EPO resistance. We also reported a highly significant relationship between genetic polymorphisms of ORAI1 and EPO resistance. The (A-A-G) haplotype of STIM1 and the (G-T-G-T-A, G-C-G-C-G, or G-T-T-C-G) haplotypes of ORAI1 were significantly associated with EPO resistance.

Genomic and phenotypic polymorphism of Clostridium botulinum Group II strain Beluga through laboratory domestication.

Laboratory domestication is the result of genetic and physiological changes of organisms acquired during numerous passages in vitro. This phenomenon has been observed in bacteria as well as in higher organisms. In an effort to understand the impact of laboratory domestication on the foodborne pathogen Clostridium botulinum and related microbial food safety research, we investigated multiple spore stocks of C. botulinum Group II Beluga from our collection, as that is a widely applied model strain used in laboratories over decades. An acquired nutrient auxotrophy was confirmed as thymidine dependency using phenotypic microarrays. In parallel, whole-genome re-sequencing of all stocks revealed a mutation in thyA encoding thymidylate synthase essential for de-novo synthesis of dTMP from dUMP in the auxotrophic stocks. A thyA-deficient Beluga variant stock was successfully complemented by introducing an intact variant of thyA and thymidine prototrophy was restored, indicating that the thymidine auxotrophy was solely due to the presence of a SNP in thyA. Our data suggested that this mutation, deleterious under nutrient-poor growth conditions in a chemically defined medium, has been present and maintained in laboratory stocks for nearly 30 years. Yet, the mutation remained unidentified since receiving the strain, most likely due to routine use of culture conditions optimized for growth performance. This work pinpoints the need for careful monitoring of model strains extensively used in laboratory settings at both phenotypic and genomic level. In applications like food safety challenge tests, compromised strains could cause incorrect predictions and thereby have deleterious consequences. To mitigate the risk of acquiring mutations, we recommend keeping passage numbers of laboratory strains low and to avoid single-colony passaging. In addition, relevant strains should be subjected to regular WGS checks and physiological validation to exclude DNA mutations with potential negative impacts on research data integrity and reproducibility.

Meat tenderness in Australian lamb: Data editing, environmental variation and their effects in genetic parameter estimation.

Breeding for meat quality increases the value of lambs and requires reliable genetic parameters to achieve balanced genetic progress. Meat tenderness, accomplished by selecting for lower shear force, is an important eating quality trait because of its relationship with consumer satisfaction. Factors influencing shear force, include the pH and temperature decline post-mortem which can contribute towards higher shear force values and increased variation across contemporary groups. This study explored if genetic parameters for shear force change when post slaughter covariates and heterogeneous variance are corrected for, using data from 32,223 animals from different sheep breeds. Results showed that removing extreme individuals and contemporary groups with high mean shear force values reduced residual variance, followed by a smaller reduction in additive genetic variance and little effect on heritability. Results show that edited data performed better at predicting progeny performance and reduced potential bias introduced in the genetic evaluation due to data quality. The effect of including post-slaughter covariates in the genetic analysis was tested by estimating different model predictability through regression of estimated breeding values against offspring performance, showing that the model including hot carcass weight performed better followed by the one including both carcass weight and C-site fat depth. Our results highlight that historic and current in-plant recording practices do not provide the capacity to account for non-genetic factors associated with abattoir environment that might be impacting the ability to accurately calculate shear force breeding values. In that sense, genetic evaluation can be improved by applying more rigorous data editing.

Whole genome re-sequencing reveals high altitude adaptation signatures and admixture in Ladakhi cattle.

Ladakhi cattle, native to the high-altitude region of Ladakh in northern India (ranging from 3,000 to 5,000 m above sea level), have evolved unique genetic adaptations to thrive in harsh environmental conditions, such as hypoxia, extreme cold, and low humidity. This study explored the genome of Ladakhi cattle to investigate genetic structure, selection signatures, and adaptive mechanisms. Whole genome sequencing reads, generated on Illumina NovaSeq 6000 platform, were aligned to the Bos taurus reference genome with BWA-MEM. SNPs were identified and filtered using GATK and bcftools, and functionally annotated with SnpEff. For population genomic analysis, PCA and admixture modeling assessed genetic structure, while Neighbor-Joining trees, LD decay, nucleotide diversity (π), and FST evaluated phylogenetic relationships and genetic variation. Selective sweeps were detected using RAiSD, and gene-set enrichment and protein-protein interaction analyses were conducted to explore functional pathways related to adaptation. The study revealed 3,759,279 unique SNPs and demonstrated that Ladakhi cattle form a distinct genetic cluster with an estimated admixture of 68 % Bos indicus and 32 % Bos taurus ancestry. Key findings include rapid linkage disequilibrium decay, low inbreeding level, and the identification of selection signatures and genes associated with hypoxia response, energy metabolism, and cold adaptation. Mean nucleotide diversity (π, 0.0037) and FST values indicated moderate genetic differentiation from other breeds. The analysis highlighted selection signatures for genes like HIF1A, ENO4, ANGPT1, EPO, NOS3, MAPK3, HMOX1, BCL2,CAMK2D, MTOR, AKT2,PIK3CB, and MAP2K1, among others, including various keratin and heat shock proteins. The interaction between genes associated with hypoxia signaling (HIF-1) and other enriched pathways such as PI3K, mTOR, NFκB, ERK, and ER stress, reveals a complex mechanism for managing hypoxic stress in Ladakhi cattle. These findings offer valuable insights for breeding programs aimed at enhancing livestock resilience in extreme environments and enhance understanding of mammalian adaptation to high-altitude conditions.

Assessing the association between common functional Nuclear Factor Kappa-b gene polymorphisms (NFKB1, NFKBIZ, NFKBIA) and Alzheimer´s disease.

The Nuclear Factor Kappa-b (NF-Κb) pathway has been implicated in the pathogenesis of Alzheimer´s disease (AD). We determined whether common variants in the NF-Κb genes were associated with the risk of developing late-onset AD (LOAD). A total of 639 Spanish LOAD and 500 controls were genotyped for the NFKB1 rs28362491/rs7667496, NFKBIA rs696, NFKBIZ rs3217713 and APOE-Ɛ2/3/4 polymorphisms. Rs7667496 C was increased in the patients (p<0.001) with the CC genotype showing a significant risk (CC vs T+, OR= 1.58, 95 %CI=1.25-2.01). The CC genotype was significantly associated with LOAD after correction by APOE-4+ genotypes, age and sex (p=0.0003, OR=1.88, 95 %CI=1.28-2.78). The NFKB1 rs28362491 I - rs7667496 C haplotype was significantly increased in the patients (p=0.02). NFKBIA and NFKBIZ variants were not associated with the risk of LOAD in our population. In conclusion, NFKB1 variants were associated with the risk of LOAD in our population. This finding encourages further studies to determine the involvement of the NF-kB components in LOAD.

Analysis of the genetic diversity of Tahe red deer and population structure of Cervus elaphu/hanglu/canadensis.

The Tahe red deer is currently the largest breeding population of antlered Cervus elaphus in China. It has unique characteristics such as drought and roughage tolerance, high antler yield and early sexual maturity. It is a high-quality provenance for cultivating high-yield Cervus elaphus breeds and is also the subject of study on the origin, evolution, and classification of Cervus elaphus. The breeding quantity of Tahe red deer has decreased significantly in recent years due to the influence of feeding conditions and consumer market. This has resulted in a serious threat to its genetic resources. To provide a scientific theoretical basis for the protection of the Tahe red deer population, we performed PCR amplification and direct sequencing of the AMELY2, DBY and SRY genes of the Y chromosome, and the ND1, COX1, ATP6, ND5, Cyt b and D-loop regions of the mtDNA, and analysed their genetic diversity and population genetic structure. The results showed high haplotype diversity and low nucleotide diversity in both the Y chromosome and mtDNA genes. The phylogenetic tree and haplotype network diagram, constructed using white-lipped deer as the outgroup, indicate that Tahe red deer has two distinct ancestral types. The phylogenetic tree, based on the Cyt b gene and D-loop region, reveals that the Cervus elaphus/hanglu/canadensis is divided into three clades: western, central, and eastern. Tahe red deer, C.h.bactrianus, and C.h.hanglu are clustered in the central clade. The study results indicate that Tahe red deer has low genetic diversity and two distinct ancestor types. It is speculated that the central clade is either the earliest differentiation from the ancestor species or the closest to it.

From the cauldron of conflict: Endogenous gene regulation by piRNA and other modes of adaptation enabled by selfish transposable elements.

Transposable elements (TEs) provide a prime example of genetic conflict because they can proliferate in genomes and populations even if they harm the host. However, numerous studies have shown that TEs, though typically harmful, can also provide fuel for adaptation. This is because they code functional sequences that can be useful for the host in which they reside. In this review, I summarize the "how" and "why" of adaptation enabled by the genetic conflict between TEs and hosts. In addition, focusing on mechanisms of TE control by small piwi-interacting RNAs (piRNAs), I highlight an indirect form of adaptation enabled by conflict. In this case, mechanisms of host defense that regulate TEs have been redeployed for endogenous gene regulation. I propose that the genetic conflict released by meiosis in early eukaryotes may have been important because, among other reasons, it spurred evolutionary innovation on multiple interwoven trajectories - on the part of hosts and also embedded genetic parasites. This form of evolution may function as a complexity generating engine that was a critical player in eukaryotic evolution.

Riboswitch Design Using MODENA.

In silico design of artificial riboswitches is a challenging and intriguing task. Since experimental approaches such as in vitro selection are time-consuming processes, computational tools that guide riboswitch design are desirable to accelerate the design process. In this chapter, we describe the usage of the MODENA web server to design ON riboswitches on the basis of a multi-objective genetic algorithm and RNA secondary structure prediction.

Sequence Design Using RNAstructure.

RNA is present in all domains of life. It was once thought to be solely involved in protein expression, but recent advances have revealed its crucial role in catalysis and gene regulation through noncoding RNA. With a growing interest in exploring RNAs with specific structures, there is an increasing focus on designing RNA structures for in vivo and in vitro experimentation and for therapeutics. The development of RNA secondary structure prediction methods has also spurred the growth of RNA design software. However, there are challenges to designing RNA sequences that meet secondary structure requirements. One major challenge is that the secondary structure design problem is likely NP-hard, making it computationally intensive. Another issue is that objective functions need to consider the folding ensemble of RNA molecules to avoid off target structures. In this chapter, we provide protocols for two software tools from the RNAstructure package: "Design" for structured RNA sequence design and "orega" for unstructured RNA sequence design.

Regulatory mechanisms and pathological implications of CYP24A1 in Vitamin D metabolism.

CYP24A1 is a crucial gene within the cytochrome P450 superfamily, responsible for encoding the enzyme 25-hydroxyvitamin D3-24-hydroxylase. This enzyme is involved in the catabolism of 1,25-dihydroxyvitamin D3, the biologically active form of vitamin D3, by hydroxylating its side chain. Through this process, CYP24A1 tightly regulates the bioavailability and physiological impact of vitamin D3 in the body. Dysregulation of CYP24A1, particularly its overexpression, has been increasingly associated with the progression of various diseases, including cancers, autoimmune disorders, and chronic inflammatory conditions. Elevated levels of CYP24A1 can lead to excessive degradation of vitamin D3, resulting in diminished levels of this critical hormone, which is essential for calcium homeostasis, immune function, and cellular proliferation. This review explores into the structural characteristics of CYP24A1, exploring how it influences its enzymatic activity. Furthermore, it examines the expression patterns of CYP24A1 across different diseases, emphasizing the enzyme's role in disease pathology. The review also discusses the regulatory mechanisms governing CYP24A1 expression, including genetic mutations, epigenetic modifications, and metabolite-mediated regulation. By understanding these mechanisms, the review provides insight into the potential therapeutic strategies that could target CYP24A1, aiming to alleviate its overexpression and restore vitamin D3 balance in disease states.

Functional analysis of LdPMAT1, a positive regulator that promotes drought tolerance in Lilium distic hum nakai.

Abiotic stress has become a major challenge for lily crop growth, development, yield and quality under irregular climate and precipitation trends. Molecular breeding is one of the most effective methods for developing highly stress-resistant cultivars. Previous studies revealed that miR396b and its target gene LdPMAT1 are involved in drought resistance, and in lily silencing miR396b significantly enhances drought resistance and LdPMAT1 expression. However, the function of LdPMAT1 in the lily response to abiotic stress is unclear. In this study, GUS activity tests and dual luciferase reporter gene assays (LUC) confirmed that LdPMAT1 is a novel miR396b target. The LdPMAT1 transcription level was greater in the roots and leaves and increased significantly within 7 days of drought stress. Stable LdPMAT1 overexpression significantly reduced leaf wilting and enhanced cell membrane stability by affecting osmoregulatory substance accumulation, improving plant drought resistance. Additionally, LdPMAT1 overexpression significantly increased the expression levels of LdCAT3 and SOD2, which encode superoxide dismutase (SOD) and catalase (CAT), respectively, as well as SOD and CAT enzyme activities. In contrast, reactive oxygen species (ROS) accumulated at high levels in the leaves and roots of the silenced plants, and the degree of damage was significantly greater than that in the wild type plants. Under conditions of 1% NaCl and 42 °C, plants overexpressing LdPMAT1 exhibited similar characteristic s of high stress resistance, with less wilting and lower ROS accumulation. This study provides a theoretical basis for cultivating new highly resistant lily cultivars and accelerating germplasm innovation to produce high-quality lilies worldwide.

CRISPR applications in microbial World: Assessing the opportunities and challenges.

Genome editing has emerged during the past few decades in the scientific research area to manipulate genetic composition, obtain desired traits, and deal with biological challenges by exploring genetic traits and their sequences at a level of precision. The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) as a genome editing tool has offered a much better understanding of cellular and molecular mechanisms. This technology emerges as one of the most promising candidates for genome editing, offering several advantages over other techniques such as high accuracy and specificity. In the microbial world, CRISPR/Cas technology enables researchers to manipulate the genetic makeup of micro-organisms, allowing them to achieve almost impossible tasks. This technology initially discovered as a bacterial defense mechanism, is now being used for gene cutting and editing to explore more of its dimensions. CRISPR/Cas 9 systems are highly efficient and flexible, leading to its widespread uses in microbial research areas. Although this technology is widely used in the scientific community, many challenges, including off-target activity, low efficiency of Homology Directed Repair (HDR), and ethical considerations, still need to be overcome before it can be widely used. As CRISPR/Cas technology has revolutionized the field of microbiology, this review article aimed to present a comprehensive overview highlighting a brief history, basic mechanisms, and its application in the microbial world along with accessing the opportunities and challenges.

Sinonasal Specific Bone Lesions, Including Fibro-Osseous and Select Odontogenic Lesions.

Sinonasal bone lesions encompass a diverse spectrum, ranging from nonneoplastic and benign conditions to aggressive, malignant neoplasms. These lesions can affect individuals across various age groups, from pediatric to adult patients. Recognizing these entities is crucial, given the variability in treatment approaches, recurrence rates, and prognoses. This review explores the common and uncommon but distinctive bone lesions affecting the sinonasal region, highlighting key clinical, radiographic, morphologic, and genetic features for each. Additionally, we provide helpful tips on distinguishing and accurately classifying each lesion within its relevant differential diagnoses.

Estimation of genetic parameters for reproductive traits in Korean dairy cattle.

Objective: In Korea, dairy cattle breeding programs have historically prioritized productive, conformation traits, leading to positive improvements, yet reproductive traits have lagged in development. This study was conducted to develop the breeding program of key reproductive traits in the Korean dairy cattle population. Methods: Utilizing data from 7,596 farms and over seven million observations, we conducted quality control to rectify manual entry errors and selected traits in line with international genetic evaluation standards. Traits analyzed included heifer conception rate (HCR), interval from calving to first insemination (CF), cow conception rate (CCR), interval from first to last insemination (FL), and days open (DO). Genetic parameters were estimated using a single trait animal model for HCR and a multiple lactation animal model for CF, CCR, FL, and DO, considering contemporary group of herd-insemination year, insemination month, and monthly age (MA) as fixed effects. Results: Results showed low heritability estimates, ranging from 0.007 to 0.035 across different traits and lactations. Theoretical reliability appears to be low on average due to the influence of heritability, but it showed sufficiently high reliability in some sires (over 0.8). In terms of genetic and phenotypic trends, capacity for reproductive traits declined for a long time until around 2014. In recent individuals, improved trend can be found. Conclusion: This study addressed the critical need for enhancing reproductive efficiency to complement the existing breeding goals, thereby supporting sustained economic viability in the dairy industry. The results underscore the need for improved data quality and methodological adjustments for reproduction records to enhance the genetic evaluation of dairy cattle in Korea.

Trends in and Predictors of Patient Pharmacogenomic Test Uptake in a National Healthcare System.

PURPOSE: Better understanding patient uptake of pharmacogenomic (PGx) testing may inform its implementation and maximize the benefits that such testing can confer. This study examined patient and provider factors associated with PGx test ordering in a national healthcare system where panel-based testing was implemented as part of routine care. METHODS: We used a retrospective matched cohort design and data from the Veterans Health Administration Corporate Data Warehouse. A conditional logistic model was used to identify factors associated with a PGx order receipt and estimate odds ratios and 95% confidence intervals. RESULTS: The following patient factors predicted receipt of a PGx test order: younger age, married status, rural residence, non-Hispanic Black or Hispanic race/ethnicity, PGx educational mailer receipt, depression diagnosis, allergy to a drug on the panel, prescriptions for drugs on the panel, and specialty care visits (p<0.05). Additionally, patients whose providers were female, younger, a nurse practitioner/physician assistant or pharmacist, or participated in an educational mailer program were more likely to receive an order (p<0.05). CONCLUSION: This study highlights factors that may facilitate or hinder the widespread and equitable implementation of PGx testing in a large national healthcare system. The information is being used to further refine the program.

Primary care provider practices, attitudes, and confidence with hereditary cancer risk assessment and testing: A mixed methods study.

PURPOSE: This study sought to better understand primary care providers' (PCPs) readiness to conduct population-based risk assessment and offer genetic testing for hereditary cancer. METHODS: Sixty PCPs completed a survey assessing their current practices, attitudes, and confidence with cancer risk assessment and testing. Sixteen participated in follow-up interviews. Descriptive statistics are presented and supported by qualitative data. RESULTS: Providers preferred direct questioning over standardized screening tools. In interviews, providers said they are not ordering cancer-risk genetic testing even when it might be appropriate. Ninety-eight percent agree testing is important to clinical care, but 73% agree that it could negatively impact patients. Ninety percent were willing to offer targeted testing, but only 68% were willing to offer population-based risk assessment. Confidence performing different behaviors necessary in a cancer risk assessment varied, with only 32% confident responding to questions specifically related to genetic testing. CONCLUSION: Providers are willing to offer genetic testing, but unlikely to do so because they lack confidence in genetics-specific skill areas. Unsystematic approaches to family history screening and fears about follow up complexity may exacerbate health disparities. Interventions to increase provider confidence in ascertaining and managing hereditary cancer are needed to achieve widespread adoption of population-based risk assessment and guideline-recommended genetic testing.

Patient experiences of cancer genetic testing by non-genetics providers in the surgical setting.

As indications for hereditary cancer genetic testing (GT) for patients with breast cancer (BC) expand, breast surgery teams offer GT to newly diagnosed patients to inform surgical plans. There is, however, limited data on the experiences of patients undergoing cancer GT by non-genetic providers. This study used in-depth interviews with 21 women recently diagnosed with BC at a large academic health system to capture their experiences. Post-positivist codebook thematic analysis was used to identify major themes from the interviews. Participants reported an overall positive experience of this GT process, stating that they prefer GT at an existing appointment shortly after their diagnosis, even though they described the conversation as brief. Many participants indicated thinking about or desiring GT before the offer was made. Interestingly, most participants did not see surgical decision-making as the main reason for GT and were instead motivated by concern for relatives and to have complete information. Interview data indicated areas for improvement in patient-provider communication, and most participants agreed that additional reference information on GT in the form of written or video materials would be helpful. Offering GT at an initial breast surgery appointment is acceptable and desired by patients with a new BC diagnosis and should be considered as a way to increase access to GT for these patients. However, additional information for patients is needed to close gaps in communication and provide a trustworthy reference following a busy medical appointment.

Genetic testing and counseling for hypertrophic cardiomyopathy: An evidence-based practice resource of the National Society of Genetic Counselors.

Hypertrophic cardiomyopathy (HCM) is a common hereditary condition affecting approximately 1 in 500 adults. It is characterized by marked clinical heterogeneity with individuals experiencing minimal to no symptoms, while others may have more severe outcomes including heart failure and sudden cardiac death. Genetic testing for HCM is increasingly available due to advances in DNA sequencing technologies and reduced costs. While a diagnosis of HCM is a well-supported indication for genetic testing and genetic counseling, incorporation of genetic services into the clinical setting is often limited outside of expert centers. As genetic counseling and testing have become more accessible and convenient, optimal integration of genomic data into the clinical care of individuals with HCM should be instituted, including delivery via genetic counseling. Drawing on recommendations from recent disease guidelines and systematic evidence reviews, we highlight key recommendations for HCM genetic testing and counseling. This practice resource provides a comprehensive framework to guide healthcare providers in the process of genetic test selection, variant classification, and cascade testing for genetic evaluation of HCM.