Genetic Testing Research Articles

Ancestral origins of TYR and OCA2 gene mutations in oculocutaneous albinism from two admixed populations in Colombia

Autosomal recessive conditions are often associated with homozygous mutations showing common ancestral origins and are frequently linked to consanguinity. However, an increasing number of compound heterozygotes are found in diverse, admixed populations. Oculocutaneous albinism (OCA) is a recessive condition caused mainly by mutations in the TYR and OCA2 genes involved in skin pigmentation. We previously screened the TYR and OCA2 genes in Colombian OCA families, identifying both known and novel mutations. Affected family members were found to be either homozygous or compound heterozygous for these gene mutations. Compound heterozygosity, where two different recessive alleles inherited from each parent lead to the expression of an autosomal recessive trait, poses a challenge in genetic diagnosis. Estimating the ancestry of these disease-associated variants, in conjunction with understanding the colonization history of admixed populations, can enhance the precision of association mapping in genetic studies. The aim of this study was to determine the ancestral origins of TYR and OCA2 mutations for OCA patients from two populations located in the Andes region of Colombia–Altiplano Cundiboyacense and Marinilla-Santuario. Comparison of OCA patients, and their unaffected relatives, with global reference populations showed a pattern of European and Native American admixture, with little African ancestry, for these two populations. Mutation-bearing TYR and OCA2 haplotypes from Colombian OCA patients were compared against haplotypes from Spanish, Native American, and Sephardic Jewish reference populations to infer their ancestral origins. For 12 OCA1 patients from the Altiplano Cundiboyacense region, 21 out of 24 mutated TYR haplotypes show Spanish origins, two show Native American origins, and one shows a Sephardic Jewish origin. The two Native American TYR haplotypes, and the single Sephardic Jewish haplotype, are all found in compound heterozygote patients, paired with the predominant Spanish TYR haplotype G47D. OCA in these three patients is a result of genetic admixture that brought together disease-causing mutations with distinct ancestral origins. Both OCA2 patients from the Marinilla-Santuario region show homozygous OCA2 mutations with a Spanish origin. These findings underscore the complexity of the genetic architecture of Mendelian disease in admixed American populations, with both consanguinity and admixture contributing to the risk of autosomal recessive OCA in Colombia.

Next-Generation Multitarget Stool DNA vs Fecal Immunochemical Test in Colorectal Cancer Screening

This diagnostic study compares the specificity and sensitivity of comercial fecal immunochemical tests with a multitarget stool DNA test.

Exploring the Molecular Interaction Between NR2E3 and NR1D1 in Retinitis Pigmentosa: A Docking and Molecular Dynamics Study

ABSTRACTBackground and AimsRetinitis pigmentosa (RP) is a hereditary retinal disorder that gradually leads to vision loss due to photoreceptor cell degeneration. This study aims to investigate the clinical features and genetic underpinnings of RP within a large Iranian family. Our focus centered on mutations in the NR2E3 gene, which plays a critical role in the development and maintenance of the retina.MethodsTwenty‐five family members showed symptoms of RP, and fourteen of them underwent clinical examinations conducted by geneticists and ophthalmologists. The DNA samples of five individuals diagnosed with RP from the family were subjected to whole‐exome sequencing (WES) as part of the study. The candidate variant identified through WES was subsequently confirmed using bidirectional sequencing in additional family members. Additionally, in silico analysis, including molecular modeling, protein–protein docking, and molecular dynamics simulation (MD), was employed to assess potential pathogenic effects associated with the candidate variants.ResultsOphthalmic examination revealed night blindness, which is a common symptom among affected individuals. Genetic analysis identified a homozygous missense variant (c.934G>A/p.R311Q) in NR2E3 exon 6, which co‐segregates with other affected family members. Furthermore, molecular docking analysis indicated potential disruption in the binding affinity between NR2E3 and NR1D1 proteins. In‐depth, molecular dynamics analysis, considering parameters such as RMSD, RMSF, and hydrogen bonding, revealed notable differences between normal and mutant protein complexes.ConclusionExploring the molecular interaction between NR2E3 and NR1D1 provides new insights into the pathogenic mechanism of the p.R311Q mutation in RP.

Is the Multitarget Stool DNA Test Just a Better “FIT” for Colorectal Cancer Screening?

Is the Multitarget Stool DNA Test Just a Better “FIT” for Colorectal Cancer Screening?

De Novo RB1 Germline Variant in Retinoblastoma with Two Subsequent Independent Neoplasms: Case Report and Literature Review

Variants in the RB1 gene are associated with retinoblastoma (RB) development, and their presence in germline cells considerably increases the risk of subsequent malignant neoplasms (SMNs) in RB survivors. We report a female patient with bilateral RB who developed two SMNs in less than ten years, with a de novo pathogenic nonsense variant in RB1 [NM_000321.3:c.306T>A, p.(Cys102*)] in heterozygosity. The updated literature review of similar cases of SMN in patients with a previous diagnosis of RB reveals a wide range in both the type of subsequent malignancy and the age at which these SMNs develop. In addition, we identified only three cases with two SMNs following RB diagnosis, with at least one of these being an EWS. This case broadens the clinical and genetic landscape of RB, demonstrates the importance of a multidisciplinary approach in these patients, and highlights genetic diagnosis as a mandatory feature for management.

Successful colonization of the testicular germinal epithelium by bone marrow stem cells producing spermatozoa of donor genotype is rare

AbstractBackgroundIt is not known whether bone marrow stem cells when injected intravenously for a bone marrow transplant colonize the human testicular epithelium. No previous studies of sperm genotype after bone marrow transplantation are reported.ObjectivesTo differentiate host from donor genotype in spermatozoa of men who have undergone successful bone marrow transplants.Materials and methodsTriplet DNA samples (spermatozoa, blood, and hair) obtained from men who had recovered sperm production after bone marrow transplant were genotyped using 44 autosomal and three sex‐related single nucleotide polymorphisms to determine the tissue genotype in pairwise comparisons of DNA profiles.ResultsParticipants were 14 men at a median of 5.5 years after allogeneic bone marrow transplant who had a median sperm output of 77 million spermatozoa/ejaculate. In 14/14 the donor (leukocyte) DNA genotype differed significantly from the spermatozoa and hair genotypes whereas hair and sperm genotypes showed no variations.DiscussionThese data suggest that paternity after a successful bone marrow transplant is likely to be of the host and not the donor's genetic origins. The study's small sample size reflects the paucity of eligible man with recovered spermatogenesis after bone marrow transplant and represents preliminary evidence. A large‐scale epidemiological analysis to estimate the frequency of bone marrow donor stem cell colonization of the testicular germinal epithelium based on progeny sex ratio and frequency of female donors is proposed.ConclusionSuccessful colonization of the testicular germinal and hair follicle epithelia by allogeneic bone marrow transplant donor stem cells is rare or does not occur.

Knowledge and perception of medical students on genetics in the genomic era.

The importance of medical genetics in modern healthcare underscores the urgent need for comprehensive genetics education for physicians. Such training should address both fundamental concepts and ethical considerations to bridge existing knowledge gaps and improve early diagnostic capabilities. In Latin America, the level of genetic knowledge among healthcare workers, particularly medical students, remains largely unexplored. This study evaluates the knowledge and attitudes toward genetic testing among final-year medical students at a public university in Monterrey, Mexico. Using a cross-sectional, observational, and anonymous survey design, the International Genetic Literacy and Attitudes Survey version 3 (iGLAS3) was administered from October 1, 2019, to August 16, 2020. This online survey collected demographic information, assessed genetic knowledge, and gauged opinions on genetic topics, focusing on items most relevant to our research objectives. Statistical analyses provided descriptive statistics and measures of central tendency. Of the 323 surveys distributed, 201 participants completed essential sections, revealing a moderate to high level of genetic knowledge, with an average score of 70 ± 11.5. The demographic profile included 58.7% women, 40.3% men, and 0.5% non-binary individuals, with an average participant age of 24years. A majority of participants expressed openness to genetic testing, primarily through private entities; however, significant concerns about the potential misuse of genetic data were noted. These findings underscore the necessity of enhancing genetic education and incorporating practical genetics training into medical curricula to meet the evolving challenges in this field effectively.

Precision medicine to identify, prevent, and treat pediatric obesity.

Pediatric obesity is a growing health concern that has many secondary adverse health implications. Personalized medicine is a tool that can be used to optimize diagnosis and treatments of many diseases. In this review, we will focus on three areas related to the genetics of pediatric obesity: (i) genetic causes predisposing to pediatric obesity, (ii) pharmacogenomics that may predict weight gain associated with pharmacotherapy, and (iii) pharmacogenomics of anti-obesity pharmacotherapy. This narrative review evaluates genetic cause of pediatric obesity and how genetic findings can be used to optimize pharmacotherapy to minimize weight gain and optimize obesity treatment in pediatric patients. Pediatric obesity has many genetic causes including genomic obesity syndromes and monogenic obesity disorders. Several genetic etiologies of obesity have current or emerging targeted genetic therapies. Pharmacogenomic (PGx) targets associated with pharmacotherapy-induced weight gain have been identified for antipsychotic, antiepileptic, antidepressant therapies, and steroids, yet to date no clinical guidelines exist for application use of PGx to tailor pharmacotherapy to avoid weight gain. As legislation evolves for genetic testing coverage and technology advances, this will decrease cost and expand access to genetic testing. This will result in identification of potential genetic causes of obesity and genes that predispose to pharmacotherapy-induced weight gain. Advances in precision medicine can ultimately lead to development of clinical practice guidelines on how to apply genetic findings to optimize pharmacotherapy to treat genetic targets of obesity and avoid weight gain as an adverse event associated with pharmacotherapy.

Exploring 17q12 Deletion Syndrome: A Case Report of Neurodevelopmental, Endocrine, and Genital Anomalies

Objective − 17q12 deletion syndrome is a rare genetic disease characterized by neurodevelopmental disorders, genital and renal abnormalities, and maturity-onset diabetes of the young type 5 (MODY5).Case Report − This case report details the case of a 13-year-old female with moderate intellectual disability, Mayer-Rokitansky-Küster-Hauser syndrome, multicystic dysplastic kidneys, and MODY5. Genetic testing revealed a 1.52-megabase heterozygous deletion on chromosome 17q12, encompassing the HNF1B and LHX1 genes, which was found to be inherited from the mother. Conclusion − This case underscores the importance of early genetic testing and multidisciplinary approach in managing the multisystemic manifestations of 17q12 deletion syndrome. Early diagnosis and appropriate management are crucial for improving the outcomes and quality of life for affected individuals.

Cytogenetic and photosynthetic responses of plants after exposure to water from a lake environment.

Plants are sensitive to environmental pollutants and are excellent organisms for genetic and physiological testing. Plant-based test systems are often used to study aquatic, aerial, and terrestrial pollution, especially Allium cepa, but studies with Tradescatia pallida specimens have gained prominence due to their sensitivity and applicability. Among the biomarkers, cytogenetic damage and chlorophyll levels are used in stress studies due to their responses to single or combined factors. The aim of this study was to evaluate cytogenetic and photosynthetic responses in T. pallida, and cytogenetic responses in A. cepa exposed to water from three sampling stations in the Juara lagoon (Municipality of Serra, ES, Brazil), collected in two sampling campaigns. The cytotoxic, genotoxic, and mutagenic potentials were analyzed using the T. pallida root tip mitosis assay and the Allium cepa test. Chloroplast pigment levels were measured in T. pallida leaves after chronic exposure to the lagoon water. The cytogenetic tests showed cytogenetic alterations at two sampling stations in at least one sampling campaign, suggesting the presence of potential pollutants, the effects of which were maximized during the rainy season. The study of photosynthetic metabolism in T. pallida showed a relationship between the levels of chloroplast pigments and the amount of nutrients present in the water.

Genetic, Clinical, and Biochemical Characterization ofa Large Cohort of Palestinian Patients With Fanconi-Bickel Syndrome.

This study aims to investigate the clinical, biochemical, and genetic characteristics of Fanconi-Bickel syndrome (FBS) in a cohort of 20 individuals from Palestine and to identify novel pathogenic variants. A retrospective analysis was conducted on medical records from Al-Makassed Hospital's pediatric department spanning 2015 to 2023. Individuals diagnosed with FBS via molecular genetic testing were included in the study. Among the 20 genetically confirmed FBS patients, hepatomegaly was prevalent in 95%, whereas 70% exhibited both developmental delay and hypophosphatemic rickets, and 68.4% experienced growth retardation. Hypertriglyceridemia (HTG) was universal. Elevated liver enzymes and alkaline phosphatase were common, along with hypophosphatemia (95%) and urinary abnormalities. Genetic analysis revealed five distinct SLC2A2 pathogenic variants, including three previously unreported variants: p.Gln23Arg (c.68A > G), p.Thr353Arg (c.1058_1059delinsGG), and an exon 7 deletion. This study presents the largest single-center cohort of FBS patients, expanding our understanding of the disorder's phenotypic and genotypic spectrum. Despite FBS generally carrying a favorable prognosis, timely diagnosis remains crucial to prevent severe complications.

Dual trigger versus human chorionic gonadotropin trigger for blastocyst quality and cumulative live birth.

To evaluate the difference in the number of euploid blastocysts and cumulative live birth rate (LBR) between dual and human chorionic gonadotropin (hCG) triggers in poor and normal ovarian responders undergoing preimplantation genetic testing (PGT) cycles. This retrospective cohort study was enrolled from July 2018 to December 2021 and followed up until June 2024 at a single reproductive medical center. Overall, 1040 in vitro fertilization (IVF)-PGT and 784 frozen-thawed embryo transfer (FET) cycles were assessed. Dual (triptorelin acetate 0.2 mg and recombinant hCG [rhCG] 250 µg) or hCG (rhCG 250 µg) trigger was used for oocyte maturation in the gonadotropin-releasing hormone antagonist protocol and PGT cycles. We assessed the embryo outcomes and FET cumulative pregnancy outcomes. The number of oocytes retrieved (10.17 ± 5.22 vs 10.27 ± 5.14, P = 0.789), MII oocytes (8.24 ± 4.26 vs 8.28 ± 4.05, P = 0.888), blastocysts (2.16 ± 1.50 vs 2.12 ± 1.49, P = 0.729), euploid blastocysts (1.06 ± 1.14 vs 1.09 ± 1.23, P = 0.726), and the rate of cumulative LBR (24.9% vs 24.9%, P = 1.000) in the dual trigger group were comparable with those in the hCG group. The trigger method was not correlated with higher LBR based on logistic regression analysis (odds ratio[OR] = 1.040 [0.778-1.392], P = 0.790). For poor and normal ovarian responders, the dual trigger, compared with the hCG trigger, did not improve the PGT embryo outcomes and FET cumulative pregnancy outcomes.

A series of genetically confirmed congenital lipodystrophy and diabetes in adult southern Indian patients.

In this study, we analysed the mutation spectrum in subjects with suspected lipodystrophy using a targeted Next-generation sequencing (NGS) approach. Subjects with suspected lipodystrophy were for screened six genes (AGPAT2, BSCL2, LMNA, PPARG, ZMPSTE24, INSR) and the variants identified were confirmed through Sanger sequencing. The clinical and biochemical parameters were compared among the mutation positive and negative subjects. We identified eight individuals with pathogenic or likely pathogenic mutations, including both homozygous and heterozygous variants. Homozygous variants included AGPAT2(NM_006412.4):c.493-2A>G, AGPAT2(NM_006412.4):c.254_258dup, and BSCL2(NM_001122955.4):c.570del, while heterozygous variants encompassed LMNA(NM_170707.4):c.1444C>T, LMNA(NM_170707.4):c.1456A>G, LMNA(NM_170707.4):c.1445G>A, and PPARG(NM_015869.5):c.949T>C mutations. In this cohort, three subjects were diagnosed with congenital generalized lipodystrophy, while the remaining five had familial partial lipodystrophy. Majority (7/8) of the patients with lipodystrophy had hepatic involvement. Notably, more than half of the subjects (5/8) achieved optimal glycemic control through insulin sensitizers (PPARγ agonist and Metformin). Interestingly, even with a limited gene panel test, mutation-positive individuals exhibited a higher prevalence of typical clinical features and biochemical characteristics associated with lipodystrophy compared to their mutation-negative counterparts. In subjects with lipodystrophy, targeted NGS based screening may establish a genetic diagnosis and aid in family screening and genetic counselling. Knowing the clinical and biochemical features typical to lipodystrophy may help in diagnosis especially in resource limited setting.

Genetic diversity of Theileria spp. in deer (Artiodactyla: Cervidae) from Brazil.

Babesia spp. and Theileria spp. are tick-borne apicomplexan protozoa that can cause disease in animals and humans. Deer are considered reservoirs for a wide variety of Piroplasmida species, including some potentially zoonotic. This study aimed to investigate the occurrence and genetic diversity of piroplasmids in wild deer sampled in four Brazilian states (São Paulo, Mato Grosso do Sul, Paraná and Goiás). For this purpose, extracted DNA samples from 181 deer buffy coat samples (138 Blastocerus dichotomus, 26 Subulo gouazoubira, 4 Mazama jucunda, 3 Mazama rufa and 10 Ozotocerus bezoarticus) were subjected to a nested PCR (nPCR) assay based on the 18S rRNA gene in order to perform a screening for piroplasmids and characterized based on the near-complete 18S rRNA, hsp70 and cox-3 genes. As a result, 75.14% (136/181) samples were positive for piroplasmids. Of these, 108 (79.41%), 101 (74.26%) and 67 (49.26%) were positive to near complete 18S rRNA, hsp70 and cox-3 genes, respectively. Phylogenetic analyses based on three molecular markers showed similar topology to each other. All sequences obtained in the present study were positioned into the Theileria sensu stricto clade, forming a distinct clade, albeit close to T. cervi. Most sequences grouped together into a large clade divided into subclades, which were often related to deer genus/species, showing that Theileria lineages seemed to show specificity according to deer genus/species. Two 18S rRNA sequences (one obtained from S. gouazoubira and another from M. jucunda) were positioned into a different clade, apart from other sequences detected in this study, indicating that different species of Theileria occur in deer from Brazil. Two subclusters were observed in the phylogenetic analysis based on the hsp70 gene: the first containing only sequences detected in marsh deer and the second grouping sequences detected in brocket deer (Mazama spp. and S. gouazoubira). The latter was also divided into smaller clades that grouped Theileria genotypes according to deer species (M. jucunda, M. rufa and S. gouazoubira). This study provides the first molecular evidence of Theileria infection in M. jucunda, as well as co-infection by distinct Theileria (sub)species/genotypes in the same deer was evidenced. Finally, this study expanded the knowledge on the diversity of Theileria spp. infecting deer from South America.

Opportunities to optimize patient experience in the in vitro fertilization (IVF) clinic and the role of genetic counselors.

To understand factors influencing patient satisfaction with genetics education and psychosocial support in an IVF clinic without a genetic counselor (GC), and how the role of a GC may fill gaps in care using a mixed-method cross-sectional study. Previous IVF patients (n = 133) completed a survey assessing satisfaction with genetics education and psychosocial support and decisional conflict about genetic testing. Kruskal-Wallis tests were used to compare satisfaction level to demographic and clinical variables. Spearman's correlation was used to analyze decisional conflict. Focus groups with 12 total participants expanded on themes identified in survey responses. Thematic analysis was performed using interpretive description. Participants reported satisfaction with their genetics education experience (78.9% somewhat or extremely satisfied). Satisfaction with genetics education was associated with satisfaction with information received about genetic testing results (H = 21.3, p < 0.01) and confidence using results in future decisions (H = 9.9, p < 0.01). Participants desired thorough pre-test and post-test counseling regarding genetic testing and directive guidance. Decision conflict about genetic testing was low (mean of 22.3, range 0-100). Satisfaction with genetics education was inversely correlated with decisional conflict (rs = - 0.42, p < 0.05). In-person GC visit scored highest among proposed education methods (mean score of 84.1). Patients felt satisfied with genetics education and psychosocial support provided by clinical providers. Gaps in care included misconceptions regarding genetic testing, a desire for more thorough counseling about genetic testing options, more directive guidance, and increased psychosocial support through external sources such as support groups.

Mainstreaming cancer genetics: feasibility of an advanced nurse practitioner-led service diagnosing Lynch syndrome from colorectal cancer in Ireland.

Colorectal cancer (CRC) is a common cancer in Ireland. Of all CRCs, 2-4% are attributable to Lynch Syndrome (LS), the most common CRC predisposition syndrome. LS is caused by constitutional pathogenic variants (PVs) affecting mismatch repair (MMR) genes with resultant MMR protein deficiency (dMMR). Screening of all CRCs with MMR immunohistochemistry (IHC) testing is advocated to increase the detection of LS. However, successful implementation requires appropriate downstream management. In Ireland the traditional pathway involves referral to cancer genetics services to assess eligibility for genetic testing. Cancer genetics services in Ireland face many challenges in providing uniform access to timely healthcare with current wait times for assessment in excess of 1 year. An increasingly adopted pathway is that of mainstreaming, whereby genetic testing is managed locally by a multidisciplinary team member. Our institution therefore implemented an Advanced Nurse Practitioner (ANP)-led service with responsibility for the LS Diagnostic Pathway and mainstream genetic testing. Data was extracted from a prospectively maintained database of all newly diagnosed CRC patients discussed at our institutions CRC multidisciplinary meeting (MDM) between January 1st, 2023, and May 31st, 2024. MMR IHC testing was performed in 97.9% of the 385 patients diagnosed with CRC. The median time from histological confirmation of CRC to the availability of the MMR IHC report was 6 days. All 51 patients (100%) who required sequential tumor testing underwent BRAF V600 ± MLH1 promoter methylation testing. Additionally, 100% of the 14 patients eligible for mainstream genetic testing were referred to the ANP-led genetics service. The median time from the initial MDM discussion to the initiation of genetic testing was 69 days, while the median time from testing to the availability of results was 19 days. Patients received their results within a median of 21 days. MMR IHC testing increases the detection of LS through identification of dMMR tumours. Successful downstream delivery of clinical services, however, requires appropriate subsequent management, in a resource-limited environment. Our institutional experience demonstrates the feasibility, efficiency, and effectiveness of an ANP-led mainstreaming model of care for hereditary colorectal cancer.

A low-fat amino acid diet reverses intestinal failure and shows good growth trends in five infants with diacylglycerol transferase 1 (DGAT1) deficiency: a prospective cohort study.

Congenital diarrheas and enteropathies (CODEs) caused by diacylglycerol transferase 1 (DGAT1) mutations often cause disease within 2 weeks after birth. If not treated properly, the disease can be life-threatening; therefore, early diagnosis and rational treatment strategies are essential. This study was conducted to improve the understanding of congenital diarrhea caused by DGAT1 deficiency. Clinical data from five congenital diarrhea infant cases caused by DGAT1 deficiency were analyzed. Infants were prospectively provided with a nutritional intervention with a low-fat amino acid formula for special medical purposes (FSMP). Their gastrointestinal symptoms and nutritional complications before and after interventions were compared. Due to poor weight gain and gastrointestinal symptoms after birth, infants were treated by our clinical nutritionist. Genetic testing confirmed a compound heterozygous mutation in DGAT1. Neither hydrolyzed nor high-medium chain triglyceride (MCT) formula significantly alleviated diarrheal symptoms; however, a low-fat amino acid diet rapidly relieved symptoms and significantly improved nutritional status, with infants showing better tolerance to dietary fat content with age. Infants with DGAT1 deficiency can be diagnosed by genetic testing. A low-fat amino acid FSMP formula and diet can quickly relieve diarrhea, vomiting, and other symptoms, and also improve infant growth and development. Ethical approval was obtained from the Medical Ethics Committee of the Children's Hospital of Fudan University (reference code: No.(2022)405).

Non-infectious mixed cryoglobulinemia as a new clinical presentation of mutation in the gene encoding coatomer subunit alpha: a case report of two adult sisters

Cryoglobulinemia is a rare disease characterized by the presence of cryoglobulins in the blood serum. It is usually caused by autoimmune, lymphoproliferative, or infectious factors. The pathogenesis of cryoglobulinemia is not well understood, therefore, genetic testing is very important. We present the case of two adult sisters with different clinical phenotypes of non-infectious cryoglobulinemic vasculitis associated with a rare genetic variant [(Hg38) 1:160323529 C&amp;gt;G, NP_004362.2:p.(Gly203Ala)]. One of the sisters suffered from essential mixed cryoglobulinemia, while the other suffered from cryoglobulinemia associated with systemic connective tissue disease. In both cases, genetic tests revealed a variant in the COPA gene, encoding coatomer subunit alpha. Mutations in the COPA gene are associated with COPA syndrome, an autoimmune interstitial lung, joint, and kidney monogenic disease, found mainly in children. Only 15 pathogenic COPA variants have been reported thus far which suggests that the full spectrum of disease manifestations remains unknown. Ours is the first report of the association of the COPA gene with non-infectious cryoglobulinemic vasculitis in adults. This unexpected finding may direct research into the pathogenesis of cryoglobulinemia and new treatment strategies for this rare disease.

Split Probe-Induced Protein Translational Amplification for Nucleic Acid Detection.

Nucleic acid detection is important in a wide range of applications, including disease diagnosis, genetic testing, biotechnological research, environmental monitoring, and forensic science. However, the application of nucleic acid detection in various fields is hindered by the lack of sensitive, accurate, and inexpensive methods. This study introduces a simple approach to enhance the sensitivity for the accurate detection of nucleic acids. Our approach combined a split-probe strategy with in vitro translational amplification of reporter protein for signal generation to detect nucleic acids with high sensitivity and selectivity. This approach enables target-mediated translational amplification of reporter proteins by linking split probes in the presence of a target microRNA (miRNA). In particular, the fluorescence split-probe sensor adopts a reporter protein with various fluorescence wavelength regions, enabling the simultaneous detection of multiple target miRNAs. Moreover, luminescence detection by merely altering the reporter protein sequence can substantially enhance the sensitivity of detection of target miRNAs. Using this system, we analyzed and quantified target miRNAs in the total RNA extracted from cell lines and cell-derived extracellular vesicles with high specificity and accuracy. This split-probe sensor has potential as a powerful tool for the simple, sensitive, and specific detection of various target nucleic acids.

BRCAIndica: a resource for ACMG/AMP classified BRCA1 and BRCA2 variants.

As genetic testing becomes increasingly accessible and affordable, the uniform and accurate interpretation of genetic variants becomes essential. The ACMG/AMP joint guidelines provide the basis for systematic and uniform interpretation of pathogenicity of genetic variants. However, the application of these in routine clinical interpretation at-scale has largely been limited by the lack of resources providing harmonized data especially at a population-scale. Here we describe BRCAIndica, a resource for BRCA1 and BRCA2 variants conforming to the ACMG & AMP joint guidelines to aid uniform clinical interpretation of genetic tests with a specific focus on variants reported in the Indian population. We collected and harmonized variants from across several resources including population-scale datasets, literature survey and other variant datasets. We then classified them according to the ACMG/AMP guidelines.We have collected a total of 10,490 unique variants, of which 2261 Pathogenic and 43 Likely Pathogenic variants belong to BRCA1 and 2694 Pathogenic and 20 Likely Pathogenic variants to BRCA2 respectively. BRCAIndica can be accessed at:https://clingen.igib.res.in/brcaindica/ . In conclusion, BRCAIndica is a powerful resource that offers researchers and clinicians with ACMG/AMP annotated BRCA variants.