Dis Model Mech. 2023 Sep 1;16(9):dmm050495. doi: 10.1242/dmm.050495. Epub 2023 Sep 22.

NO ABSTRACT

PMID:37737037 | DOI:10.1242/dmm.050495

Tomography. 2023 Sep 4;9(5):1694-1710. doi: 10.3390/tomography9050135.

ABSTRACT

Anal cancer is a rare disease, but its incidence has been increasing steadily. Primary staging and assessment after chemoradiation therapy are commonly performed using MRI, which is considered to be the preferred imaging modality. CT and PET/CT are useful in evaluating lymph node metastases and distant metastatic disease. Anal squamous-cell carcinoma (ASCC) and rectal adenocarcinoma are typically indistinguishable on MRI, and a biopsy prior to imaging is necessary to accurately stage the tumor and determine the treatment approach. This review discusses the histology, MR technique, diagnosis, staging, and treatment of anal cancer, with a particular focus on the differences in TNM staging between anal and rectal carcinomas.

PURPOSE: This review discusses the histology, MR technique, diagnosis, staging, and treatment of anal cancer, with a particular focus on the differences in TNM staging between anal squamous-cell carcinoma (ASCC) and rectal adenocarcinoma.

METHODS AND MATERIALS: To conduct this updated review, a comprehensive literature search was performed using prominent medical databases, including PubMed and Embase. The search was limited to articles published within the last 10 years (2013-2023) to ensure their relevance to the current state of knowledge.

INCLUSION CRITERIA: (1) articles that provided substantial information on the diagnostic techniques used for ASCC, mainly focusing on imaging, were included; (2) studies reporting on emerging technologies; (3) English-language articles.

EXCLUSION CRITERIA: articles that did not meet the inclusion criteria, case reports, or articles with insufficient data. The primary outcome of this review is to assess the accuracy and efficacy of different diagnostic modalities, including CT, MRI, and PET, in diagnosing ASCC. The secondary outcomes are as follows: (1) to identify any advancements or innovations in diagnostic techniques for ASCC over the past decade; (2) to highlight the challenges and limitations of the diagnostic process.

RESULTS: ASCC is a rare disease; however, its incidence has been steadily increasing. Primary staging and assessment after chemoradiation therapy are commonly performed using MRI, which is considered to be the preferred imaging modality. CT and PET/CT are useful in evaluating lymph node metastases and distant metastatic disease.

CONCLUSION: ASCC and rectal adenocarcinoma are the most common histological subtypes and are typically indistinguishable on MRI; therefore, a biopsy prior to imaging is necessary to stage the tumor accurately and determine the treatment approach.

PMID:37736988 | PMC:PMC10514831 | DOI:10.3390/tomography9050135

Oncologist. 2023 Sep 20:oyad263. doi: 10.1093/oncolo/oyad263. Online ahead of print.

ABSTRACT

Appendiceal cancer is a rare, orphan disease with no therapies currently approved by the FDA for its treatment. Given the limited data regarding drug efficacy, these tumors have historically been treated with chemotherapy designed for colon cancer. However, an overwhelming body of molecular data has demonstrated that appendiceal adenocarcinoma is a distinct entity with key molecular differences from colon cancer, notably rare APC mutation. Recognizing that APC loss-of-function is thought to contribute to taxane resistance and that taxanes are effective in the treatment of other gastrointestinal tumors, including gastric, esophageal, and small bowel adenocarcinoma, we completed a single-center retrospective study to assess efficacy. In a cohort of 13 patients with metastatic appendiceal adenocarcinoma, treated with taxane chemotherapy the median overall survival was 8.8 months. Of 10 evaluable patients, we observed 3 responses, 4 patients with stable disease, and 3 with progression (30% response rate, 70% disease control rate). The results of this study showing activity of taxane-based chemotherapy in appendiceal adenocarcinoma support further clinical investigation of taxane therapy in this orphan disease.

PMID:37738316 | DOI:10.1093/oncolo/oyad263

Cas Lek Cesk. 2023 Summer;162(4):136-147.

ABSTRACT

Hypoparathyroidism is a rare endocrine disease caused by an absence or insufficient production of parathormone. Parathormone deficiency leads to lower serum calcium concentration that is responsible for patients' neuromuscular symptoms. Conventional treatment consists of calcium and active vitamin D metabolites administration but doesn't constitute an adequate substitution of missing parathormone. Although the treatment substantially alleviates patients' troubles, chronic complications may develop because of hyperphosphatemia and conventional medication. Solution to this resides in recombinant parathormone administration, however the only one drug available is being now recalled from the market. The mainstay of hypoparathyroidism prevention is the judicious indication of total thyroidectomy representing the main cause of the disease.

PMID:37734939

Hum Genet. 2023 Nov;142(11):1561-1569. doi: 10.1007/s00439-023-02592-8. Epub 2023 Sep 20.

ABSTRACT

Exome and genome sequencing (ES/GS) in genetic medicine and research leads to discovering genomic secondary findings (SFs) unrelated to the purpose of the primary test. There is a lack of agreement to return the SF results for individuals undergoing the test. The aim of this study is to investigate the frequency of actionable secondary findings using GS data obtained from the rare disease study and the Korean Genome and Epidemiology Study (KoGES) in the National Project of Bio Big Data pilot study. Pathogenic (P) or likely pathogenic (LP) variants of 78 SF genes recommended by the American College of Medical Genetics and Genomics (ACMG) were screened in the rare disease study and KoGES. The pathogenicity of SF gene variants was determined according to the ACMG interpretation. The overall SF rate was 3.75% for 280 individuals with 298 P/LP variants of 41 ACMG SF genes which were identified among 7472 study participants. The frequencies of genes associated with cardiovascular, cancer, and miscellaneous phenotypes were 2.17%, 1.22%, and 0.58%, respectively. The most frequent SF gene was TTN followed by BRCA2. The frequency of actionable SFs among participants with rare disease and general population participants in the Korean population presented here will assist in reporting results of medically actionable SFs in genomic medicine.

PMID:37728764 | DOI:10.1007/s00439-023-02592-8

Pol J Pathol. 2023;74(2):141-143. doi: 10.5114/pjp.2023.128787.

ABSTRACT

Ectopic mammary gland tissue in the vulva is an exceptionally rare disease. We present a case of a 62-year-old woman with a left vulvar mass of 30 years duration that progressively increased in size. The patient reported having pressure and discomfort, especially during movement. Surgical excision was performed, and a histopathological examination revealed a well-differentiated ectopic breast. We also review other cases of vulvar ectopic breast to further comprehend the characteristics of this rare disease. Clinicians and pathologists should always consider it as a differential diagnosis when presented with a vulvar mass.

PMID:37728473 | DOI:10.5114/pjp.2023.128787

Am J Case Rep. 2023 Sep 20;24:e940990. doi: 10.12659/AJCR.940990.

ABSTRACT

BACKGROUND Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitic condition characterized by bronchial asthma and eosinophilia. While biliary involvement is uncommon in EGPA, we present a unique case of EGPA presenting as steroid-responsive sclerosing cholangitis and cholecystitis. This case highlights the importance of considering EGPA in the differential diagnosis of biliary diseases, especially in patients with a history of bronchial asthma. CASE REPORT A 47-year-old man with a history of bronchial asthma presented with fatigue, weight loss, and epigastralgia. Blood tests revealed eosinophilia and elevated inflammatory markers, leading to the diagnosis of EGPA. Further imaging studies, including magnetic resonance cholangiopancreatography and contrast-enhanced computed tomography, confirmed the presence of sclerosing cholangitis and cholecystitis, a rare manifestation of EGPA. CONCLUSIONS Prompt treatment with prednisolone and azathioprine resulted in remission of symptoms and resolution of cholangitis and cholecystitis in this case. Our findings emphasize the importance of early recognition and appropriate management of EGPA-associated biliary involvement. Increased awareness of this rare manifestation may facilitate timely diagnosis and improve patient outcomes.

PMID:37726949 | DOI:10.12659/AJCR.940990

BMJ Case Rep. 2023 Sep 18;16(9):e252667. doi: 10.1136/bcr-2022-252667.

ABSTRACT

Pycnodysostosis is a rare genetic condition that leads to generalised bony sclerosis and increased fracture risk. Orthopaedic specialists play a crucial role in managing affected children due to their susceptibility to frequent fractures. We had a case of a middle childhood female patient with pycnodysostosis and a femur fracture. Initially, an attempt using the Titanium Elastic Nailing System was made, but the sclerotic metaphyseal bone made it challenging. So, we opted for a 4.5 mm locked compressive plate, with multiple drill bits as a backup due to potential drill breakage. Though elastic nailing is preferred for paediatric long bone fractures, surgeons must be prepared for extremely sclerotic cortices and a narrow medullary canal when dealing with patients with pycnodysostosis. Open fixation and multiple drill bits in the toolkit are essential to overcome the potential obstacles during the procedure.

PMID:37723084 | DOI:10.1136/bcr-2022-252667

Mol Genet Metab. 2023 Aug 30;140(3):107693. doi: 10.1016/j.ymgme.2023.107693. Online ahead of print.

ABSTRACT

Newborn screening (NBS) began a revolution in the management of biochemical genetic diseases, greatly increasing the number of patients for whom dietary therapy would be beneficial in preventing complications in phenylketonuria as well as in a few similar disorders. The advent of next generation sequencing and expansion of NBS have markedly increased the number of biochemical genetic diseases as well as the number of patients identified each year. With the avalanche of new and proposed therapies, a second wave of options for the treatment of biochemical genetic disorders has emerged. These therapies range from simple substrate reduction to enzyme replacement, and now ex vivo gene therapy with autologous cell transplantation. In some instances, it may be optimal to introduce nucleic acid therapy during the prenatal period to avoid fetopathy. However, as with any new therapy, complications may occur. It is important for physicians and other caregivers, along with ethicists, to determine what new therapies might be beneficial to the patient, and which therapies have to be avoided for those individuals who have less severe problems and for which standard treatments are available. The purpose of this review is to discuss the "Standard" treatment plans that have been in place for many years and to identify the newest and upcoming therapies, to assist the physician and other healthcare workers in making the right decisions regarding the initiation of both the "Standard" and new therapies. We have utilized several diseases to illustrate the applications of these different modalities and discussed for which disorders they may be suitable. The future is bright, but optimal care of the patient, including and especially the newborn infant, requires a deep knowledge of the disease process and careful consideration of the necessary treatment plan, not just based on the different genetic defects but also with regards to different variants within a gene itself.

PMID:37716025 | DOI:10.1016/j.ymgme.2023.107693

Medicina (B Aires). 2023 Sep;83 Suppl 4:52-56.

ABSTRACT

Rare diseases and undiagnosed diseases have recently positioned themselves as clinical entities that provide important opportunities to advance our understanding of gene functions and the impact of them in the individual development. In this review, we present how efforts made over years to understand common diseases, rare diseases and even undiagnosed diseases come together today to cooperatively advances scientific knowledge. These advance in science and new acquired knowledge, make possible to apply the advances obtained in a group of clinical conditions to others with similar phenotypic characteristics or vice versa. The cooperative work of multidisciplinary teams and the communication between clinicians and researchers have and will provide opportunities for better treatments for patients and families across multiple common and rare diseases.

PMID:37714123

Eur J Pediatr. 2023 Sep 14. doi: 10.1007/s00431-023-05167-x. Online ahead of print.

ABSTRACT

Delay in diagnosing multidrug-resistant tuberculosis (MDR-pTB) in children prolongs time to effective treatment. Data on risk factors for pediatric MDR from low-incidence countries are scarce. Retrospective nationwide case-control study to analyze MDR-pTB cases in Germany between 2010 and 2020 in comparison to a drug-susceptible (DS)-pTB group. We included 52 MDR cases (24 tuberculosis (TB), 28 TB infection (TBI); mean age 7.3 years) and 56 DS cases (31 TB, 26 TBI; mean age 7.9 years). Groups were similar for sex, household size, and migration background. Compared to the DS group, more children with MDR were born in the Commonwealth of Independent States (CIS) (22% MDR-pTB vs. 13% DS-pTB, n.s.) and had more MDR index cases (94% MDR-pTB, 5% DS-pTB, p < 0.001). The interval between first healthcare contact and initiation of effective therapy was significantly longer in MDR-pTB (47 days) than in DS-pTB (11 days, p < 0.001), correlating with disease progression. Treatment for MDR-pTB was successful in 74%, but 22% experienced long-term adverse effects (e.g., hepatopathy, hearing loss).

CONCLUSIONS: Close contact to MDR cases or birth in MDR-TB-high-incidence countries are risk factors for MDR-pTB. Early identification of potential MDR index cases by contact investigation, and susceptibility testing in children from high-burden MDR-TB countries are essential for timely diagnosis and treatment, reducing the severity of disease and treatment side effects.

TRIAL REGISTRATION: Deutsches Register Klinischer Studien ( https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023817 ), DRKS00023817, 2020-09-08.

WHAT IS KNOWN: •Management of children with MDR-TB remains challenging due to difficulties in diagnosing MDR-TB (lack of information on MDR index case, lack of microbiological confirmation in paucibacillary disease). •Choice of treatment regimen and monitoring of side effects.

WHAT IS NEW: •Children with an MDR-TB index or born in a MDR-TB-high-incidence country are at higher risk of developing MDR-TB in a low incidence country. •The time lag to initiate treatment in MDR-TB is longer than in DS-TB and MDR-TB treatment involves a higher risk of adverse effects in longer treatment regimens especially with injectables.

PMID:37707590 | DOI:10.1007/s00431-023-05167-x

BMC Ophthalmol. 2023 Sep 13;23(1):375. doi: 10.1186/s12886-023-03104-y.

ABSTRACT

BACKGROUND: In cases with advanced glaucomatous disc changes, further changes associated with other optic neuropathies cannot be easily identified. We present a case of preexisting open-angle glaucoma and concurrent involvement of sarcoidosis-associated optic neuropathy.

CASE PRESENTATION: A 53-year-old man presented with gradual visual loss in his left eye, which began 1 year ago and accelerated 3 months ago. The best-corrected visual acuity in the right eye was 20/20 and counting fingers in the left. Intraocular pressures (IOP) were 12 mmHg in the right eye and 34 mmHg in the left. We diagnosed him with advanced open-angle glaucoma in the left eye based on the advanced glaucomatous cupping of the left optic disc. The IOP in the left eye dropped to 10 mmHg and was well controlled with antiglaucomatous medication; however, his left optic disc developed pallor 3 months after the treatment. The patient was revealed to be diagnosed with sarcoidosis a month ago and had been treated with systemic corticosteroids thereafter by a pulmonologist. Orbital magnetic resonance imaging revealed sarcoidosis-associated optic neuropathy in the left eye. Subsequently, optic neuropathy occurred in his right eye.

CONCLUSIONS: In eyes with advanced glaucomatous disc change, detecting the coexistence of other optic neuropathies can be difficult. This report highlights the importance of careful ophthalmic examinations and investigation for etiologies of other optic neuropathies if non-glaucomatous changes are suspected even in eyes with advanced glaucoma.

PMID:37704998 | DOI:10.1186/s12886-023-03104-y

EMBO Mol Med. 2023 Sep 13:e17833. doi: 10.15252/emmm.202317833. Online ahead of print.

ABSTRACT

Snyder-Robinson syndrome (SRS) results from mutations in spermine synthase (SMS), which converts the polyamine spermidine into spermine. Affecting primarily males, common manifestations of SRS include intellectual disability, osteoporosis, hypotonia, and seizures. Symptom management is the only treatment. Reduced SMS activity causes spermidine accumulation while spermine levels are reduced. The resulting exaggerated spermidine:spermine ratio is a biochemical hallmark of SRS that tends to correlate with symptom severity. Our studies aim to pharmacologically manipulate polyamine metabolism to correct this imbalance as a therapeutic strategy for SRS. Here we report the repurposing of 2-difluoromethylornithine (DFMO), an FDA-approved inhibitor of polyamine biosynthesis, in rebalancing spermidine:spermine ratios in SRS patient cells. Mechanistic in vitro studies demonstrate that, while reducing spermidine biosynthesis, DFMO also stimulates the conversion of spermidine into spermine in hypomorphic SMS cells and induces uptake of exogenous spermine, altogether reducing the aberrant ratios. In a Drosophila SRS model characterized by reduced lifespan, DFMO improves longevity. As nearly all SRS patient mutations are hypomorphic, these studies form a strong foundation for translational studies with significant therapeutic potential.

PMID:37702369 | DOI:10.15252/emmm.202317833

Orphanet J Rare Dis. 2023 Sep 12;18(1):287. doi: 10.1186/s13023-023-02753-y.

ABSTRACT

BACKGROUND: We consider two key challenges that early-stage biotechnology firms face in developing a sustainable financing strategy and a sustainable business model: developing a valuation model for drug compounds, and choosing an appropriate operating model and corporate structure. We use the specific example of Unravel Biosciences-a therapeutics platform company that identifies novel drug targets through off-target mechanisms of existing drugs and then develops optimized new molecules-throughout the paper and explore a specific scenario of drug repurposing for rare genetic diseases.

RESULTS: The first challenge consists of producing a realistic financial valuation of a potential rare disease repurposed drug compound, in this case targeting Rett syndrome. More generally, we develop a framework to value a portfolio of pairwise correlated rare disease compounds in early-stage development and quantify its risk profile. We estimate the probability of a negative return to be [Formula: see text] for a single compound and [Formula: see text] for a portfolio of 8 drugs. The probability of selling the project at a loss decreases from [Formula: see text] (phase 3) for a single compound to [Formula: see text] (phase 3) for the 8-drug portfolio. For the second challenge, we find that the choice of operating model and corporate structure is crucial for early-stage biotech startups and illustrate this point with three concrete examples.

CONCLUSIONS: Repurposing existing compounds offers important advantages that could help early-stage biotech startups better align their business and financing issues with their scientific and medical objectives, enter a space that is not occupied by large pharmaceutical companies, and accelerate the validation of their drug development platform.

PMID:37700316 | DOI:10.1186/s13023-023-02753-y

BMJ Case Rep. 2023 Sep 12;16(9):e255346. doi: 10.1136/bcr-2023-255346.

ABSTRACT

Pulmonary sequestration is a rare congenital condition. It is a dysplastic lung tissue with a separate systemic blood supply and without a bronchial tree connection. The emergence of a superimposed infection can lead to its diagnosis, such as Staphylococcus aureus, Pseudomonas aeruginosa, Nocardia asteroids and Aspergillus sp pneumonia. Mycobacterium avium complex (MAC) superimposed disease is exceedingly rare. We report a case of a man in his third decade without known medical disorders presenting with a persistent cough. After an extensive microbiological workup, an MAC infection was diagnosed. An elevated carbohydrate antigen 19-9 (CA 19-9) was also noted. He was treated with antimycobacterial therapy and lobectomy resulting in clinical improvement and CA19-9 normalisation. This case illustrates the value of comprehensive microbiological investigations in patients with chronic respiratory symptoms and imaging findings that are not typical of bacterial pneumonia. Clinical studies remain needed to investigate the utility of CA 19-9 in a scoring system to guide MAC therapy.

PMID:37699740 | DOI:10.1136/bcr-2023-255346

Lancet Respir Med. 2023 Sep 8:S2213-2600(23)00297-7. doi: 10.1016/S2213-2600(23)00297-7. Online ahead of print.

ABSTRACT

The growing use of modulator therapies aimed at restoring cystic fibrosis transmembrane conductance regulator (CFTR) protein function in people with cystic fibrosis has fundamentally altered clinical trial strategies needed to advance new therapeutics across an orphan disease population that is now divided by CFTR modulator eligibility. The development of a robust pipeline of nucleic acid-based therapies (NABTs)-initially directed towards the estimated 10% of the cystic fibrosis population who are genetically ineligible for, or intolerant of, CFTR modulators-is dependent on the optimisation of restricted trial participant resources across multiple development programmes, a challenge that will preclude the use of gold standard placebo-controlled trials. Advancement of a full pipeline of symptomatic therapies across the entire cystic fibrosis population will be challenged by smaller effect sizes and uncertainty regarding their clinical importance in a growing modulator-treated population with more mild and stable pulmonary disease. In this Series paper, we aim to lay the foundation for clinical trial strategy and community partnership that must deviate from established and familiar precedent to advance the future pipeline of cystic fibrosis therapeutics.

PMID:37699421 | DOI:10.1016/S2213-2600(23)00297-7

Eur J Endocrinol. 2023 Sep 1;189(3):387-395. doi: 10.1093/ejendo/lvad128.

ABSTRACT

OBJECTIVE: Our study aimed to assess the impact of genetic modifiers on the significant variation in phenotype that is observed in individuals with SHOX deficiency, which is the most prevalent monogenic cause of short stature.

DESIGN AND METHODS: We performed a genetic analysis in 98 individuals from 48 families with SHOX deficiency with a target panel designed to capture the entire SHOX genomic region and 114 other genes that modulate growth and/or SHOX action. We prioritized rare potentially deleterious variants.

RESULTS: We did not identify potential deleterious variants in the promoter or intronic regions of the SHOX genomic locus. In contrast, we found eight heterozygous variants in 11 individuals from nine families in genes with a potential role as genetic modifiers. In addition to a previously described likely pathogenic (LP) variant in CYP26C1 observed in two families, we identified LP variants in PTHLH and ACAN, and variants of uncertain significance in NPR2, RUNX2, and TP53 in more affected individuals from families with SHOX deficiency. Families with a SHOX alteration restricted to the regulatory region had a higher prevalence of a second likely pathogenic variant (27%) than families with an alteration compromising the SHOX coding region (2.9%, P = .04).

CONCLUSION: In conclusion, variants in genes related to the growth plate have a potential role as genetic modifiers of the phenotype in individuals with SHOX deficiency. In individuals with SHOX alterations restricted to the regulatory region, a second alteration could be critical to determine the penetrance and expression of the phenotype.

PMID:37695807 | DOI:10.1093/ejendo/lvad128

Hum Gene Ther. 2023 Sep;34(17-18):763-775. doi: 10.1089/hum.2023.152.

ABSTRACT

The development of viral vectors and recombinant DNA technology since the 1960s has enabled gene therapy to become a real therapeutic option for several inherited and acquired diseases. After several ups and downs in the gene therapy field, we are currently living a new era in the history of medicine in which several ex vivo and in vivo gene therapies have reached maturity. This is testified by the recent marketing authorization of several gene therapy medicinal products. In addition, many others are currently under evaluation after exhaustive investigation in human clinical trials. In this review, we summarize some of the most significant milestones in the development of gene therapy medicinal products that have already facilitated the treatment of a significant number of rare diseases. Despite progresses in the gene therapy field, the transfer of these innovative therapies to clinical practice is also finding important restrictions. Advances and also challenges in the progress of gene therapy for rare diseases are discussed in this opening review of a Human Gene Therapy issue dedicated to the 30th annual Congress of the European Society for Gene and Cell Therapy.

PMID:37694572 | DOI:10.1089/hum.2023.152

Orphanet J Rare Dis. 2023 Sep 11;18(1):285. doi: 10.1186/s13023-023-02912-1.

ABSTRACT

Necessity driven organisational change in the post-pandemic landscape has seen health care providers adopting innovations to manage and process health data. These include the use of 'real-world' datasets of routinely collected clinical information, enabling data-driven delivery. Rare disease risks being 'left-behind' unless our clinical and research communities engage with the challenges and opportunities afforded by the burgeoning field of health data informatics. We address the challenges to the meaningful use and reuse of rare disease data, and, through a series of recommendations around workforce education, harmonisation of taxonomy, and ensuring an inclusive health data environment, we highlight the role that those who manage rare disease must play in addressing them.

PMID:37697298 | PMC:PMC10496203 | DOI:10.1186/s13023-023-02912-1

Brain Nerve. 2023 Sep;75(9):1065-1070. doi: 10.11477/mf.1416202473.

ABSTRACT

The Initiative on Rare and Undiagnosed Diseases (IRUD) was a project for patients who remain undiagnosed after undergoing various clinical tests. This project includes both the clinical aspect of diagnosing rare diseases and the research aspect of identifying new diseases. Since 2015, the diagnosis rate for undiagnosed patients has been 40-50%. From a clinical perspective, this project demonstrated how genome analysis has become indispensable in rare diseases, especially in pediatrics. From a research standpoint, over 30 diseases have been identified through this project. This project was coordinated with a similar undiagnosed disease program from outside the country, and we strongly believe that much success has been achieved. Future challenges include examining which approaches (e.g., long-read genome analysis, transcriptome analysis, and methylation analysis) would be effective for undiagnosed patients after exome analysis, and developing therapeutic drugs for rare diseases. Future challenges include addressing the approximately 50% of patients whose undiagnosed diseases cannot be diagnosed even after exome analysis and developing therapeutic agents for the rare diseases that have been diagnosed.

PMID:37691248 | DOI:10.11477/mf.1416202473