The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual\'s genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner\'s fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies.

Alkaptonuria is a rare autosomal recessive congenital disorder of metabolism that affects 1 in 250,000 live births. It manifests as ochronosis and degenerative arthritis due to the accumulation of homogentistic acid in cartilage and heart valves along with precipitation of renal, salivary, pancreatic and gall bladder calculi. It is noted to cause cardiac valve stenosis and regurgitation secondary to calcification leading to cardiac failure in 10% of patients. Through this report, we present a successful perioperative anaesthetic management of a 74-year-old man with cardiac ochronosis, who underwent an aortic valve replacement with coronary artery bypass graft surgery at our centre.

Osteochondrosis (OC) is a developmental orthopaedic disease of significant concern in numerous sport horse breeds, with significant international relevance. Using digital radiographs, we assessed the occurrence of hock (tarsocrural joint) OC in 3 048 Pura Raza Española (PRE) horses which took part in a morpho-functional test, in three specific locations in the tarsus limbs: the Distal Intermediate Ridge of the Tibia (DIRT), the lateral trochlear ridges of the talus (LTT), and the medial trochlear ridges of the talus (MTT). An incidence rate of 13.3% was found for hock OC in the analysed sample, with the highest incidence rate observed in DIRT (10.0%) and the lowest in MTT (0.2%). Estimates of genetic predisposition to hock OC were carried out using three genetic approaches: 1a) a binomial threshold model based on the presence or absence of OC, 1b) a multinomial threshold model, on a scale from 0 (absence) to 3 (maximum), and 2) a linear model. The effects considered in the models included sex, genetic origin and stud class. All the analyses were based on the Bayesian inference methodology, using the THRGIBBS3F90 software. The binomial threshold model yielded the most suitable results, with an estimated heritability for Overall hock OC of 0.71 ± 0.055 on the underlying scale (0.53 on the observed scale), ranging in different locations from 0.48 ± 0.087 (LTT) to 0.66 ± 0.063 (DIRT) on the underlying scale (0.10 and 0.38 on the observed scale, respectively). The highest significative genetic correlation was observed between Overall and DIRT (0.97) for approach 1a, and the lowest significant genetic correlation was between Overall and LTT (0.49), for approach 2. This study contributes valuable insights into the genetic predisposition towards, as well as for the potential for selective breeding against, hock OC in PRE horses, and provides a basis for future research and breeding programmes aimed at minimising the occurrence of hock OC and promoting the overall health of this breed.

BACKGROUND: Exercise-induced pulmonary haemorrhage (EIPH) in athletic horses is characterized by the presence of blood from the lungs in the tracheobronchial tree after intense exercise. Despite the high prevalence of EIPH in horses, the primary aetiology remains unknown. Variants in the genes encoding CD39 and CD39L1 (ENTPD1 and ENTPD2, respectively) were previously reported as potential genetic causes involved in EIPH pathogenesis. However, the role of these variants in haemostatic functions is unknown.
RESULTS: To investigate the association between EIPH and missense variants in the ENTPD1 (rs1152296272, rs68621348, and rs68621347) and ENTPD2 genes (rs782872967), 76 Thoroughbred horses diagnosed with EIPH and 56 without clinical signs of EIPH (control group) by trachea-bronchial endoscopy were genotyped. The rs1152296272 and rs68621347 variants were linked, which explained why the same results were found in all horses. Approximately 96% and 95% of the EIPH and control horses, respectively, carried at least one nonreference allele for these variants. In contrast, 100% of the control horses and 96% of the EIPH horses were homozygous for the reference allele for the rs68621348 variant. In the EIPH group, 1.5% of the horses were homozygotes and 24% were heterozygous for the nonreference allele of the rs782872967 variant. In the control group, the nonreference allele of this variant was observed only in heterozygotes (16%). There were no significant differences between groups for any of the variants.
CONCLUSIONS: The variants previously described in the genes encoding the CD39 and CD39L1 enzymes were highly present in the studied population. However, no association was found between the occurrence of EIPH and the presence of these variants in Thoroughbred horses in this study.

UNASSIGNED: Real-world analyses on burden of illness in patients with alpha-1 antitrypsin deficiency (AATD) are limited. We investigated the real-world burden of liver-related clinical events among adult and pediatric patients with AATD in the USA.
UNASSIGNED: This was a retrospective, observational analysis of administrative claims data from the IQVIA PharMetrics® Plus and Ambulatory Electronic Medical Records databases from 2011 to 2022. Patients had a diagnosis of liver and/or lung disease with ≥180 days of continuous enrollment in the IQVIA PharMetrics Plus database before and ≥90 days after their first diagnosis. Follow-up time was assigned to the AATD with liver disease health state or AATD with both liver and lung disease health state (for patients aged ≥18 years only). Baseline demographic characteristics and liver-related clinical events of interest were reported.
UNASSIGNED: Of 5136 eligible patients, 771 adult and 123 pediatric patients contributed time to the AATD with liver disease health state; 541 adults contributed time to the AATD with both liver and lung disease health state. Among adults, patients with both liver and lung disease had higher rates of liver-related clinical events than patients with liver disease alone. Ascites was the most frequently observed clinical event among adults in both health states, and the median time to the composite of any liver-related clinical event was 26.5 days among all adults combined. Across all pediatric age groups, ascites, gastrointestinal bleed and hepatic encephalopathy were more common than spontaneous bacterial peritonitis and hepatocellular carcinoma, but median time to liver-related clinical event varied by age group at index date and type of event. No liver transplantations occurred in patients aged 6-17 years.
UNASSIGNED: Diagnosed AATD with liver disease carries a substantial burden on adult and pediatric patients; new treatment options are warranted to avoid disease progression to decompensating events.

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The Na,K-ATPase is an α-β heterodimer. It is well known that the Na,K-ATPase β subunit is required for the biosynthesis and trafficking of the α subunit to the plasma membrane. During investigation of properties of human ATP1A3 mutations in 293 cells, we observed a reciprocal loss of endogenous ATP1A1 when expressing ATP1A3. Scattered reports going back as far as 1991 have shown that experimental expression of one subunit can result in reduction in another, suggesting that the total amount is strictly limited. It seems logical that either α or β subunit should be rate-limiting for assembly and functional expression. Here, we present evidence that neither α nor β may be limiting and that there is another level of control that limits the amount of Na,K-ATPase to physiological levels. We propose that α subunits compete for something specific, like a private chaperone, required to finalize their biosynthesis or to prevent their degradation in the endoplasmic reticulum.

暂无摘要。

UNASSIGNED: Many loci segregate alleles classified as \"genetic diseases\" due to their deleterious effects on health. However, some disease alleles have been reported to show beneficial effects under certain conditions or in certain populations. The beneficial effects of these antagonistically pleiotropic alleles may explain their continued prevalence, but the degree to which antagonistic pleiotropy is common or rare is unresolved. We surveyed the medical literature to identify examples of antagonistic pleiotropy to help determine whether antagonistic pleiotropy appears to be rare or common.
UNASSIGNED: We identified ten examples of loci with polymorphisms for which the presence of antagonistic pleiotropy is well supported by detailed genetic or epidemiological information in humans. One additional locus was identified for which the supporting evidence comes from animal studies. These examples complement over 20 others reported in other reviews.
UNASSIGNED: The existence of more than 30 identified antagonistically pleiotropic human disease alleles suggests that this phenomenon may be widespread. This poses important implications for both our understanding of human evolutionary genetics and our approaches to clinical treatment and disease prevention, especially therapies based on genetic modification.

The International Committee on Classification of Corneal Dystrophies (IC3D) was founded in 2005 to address difficulties arising from the outdated nomenclature for corneal dystrophies (CD) and to correct misconceptions in the literature. For each of the 22 CDs, a separate template was created to represent the current clinical, pathological and genetic knowledge of the disease. In addition, each template contains representative clinical photographs as well as light and electron microscopic images and, if available, confocal microscopic and coherence tomographic images of the respective CD. After the first edition was published in 2008, the revised version followed in 2015. The third edition of the IC3D was published as open access in February 2024. The latest edition is intended to serve as a reference work in everyday clinical practice and facilitate the diagnosis of CD, which might sometimes be difficult. This article provides an overview of the diagnostic and treatment principles of CD and presents the IC3D and its changes over time.
UNASSIGNED: Das Internationale Komitee für die Klassifikation von Hornhautdystrophien („International Committee on Classification of Corneal Dystrophies“ [IC3D]) wurde im Jahr 2005 gegründet, um Schwierigkeiten zu beseitigen, die sich aus der veralteten Nomenklatur für Hornhautdystrophien (HD) ergaben, und um Fehleinschätzungen in der Literatur zu korrigieren. Für jede der 22 HD wurde eine eigene Vorlage (sog. „Template“) erstellt, die den aktuellen klinischen, pathologischen und genetischen Wissensstand über die Erkrankung widerspiegelt. Darüber hinaus enthält jedes „Template“ repräsentative klinische Fotografien sowie licht- und elektronenmikroskopische Bilder und, falls vorhanden, konfokalmikroskopische und kohärenztomographische Aufnahmen der jeweiligen HD. Nach Veröffentlichung der ersten Ausgabe im Jahr 2008 folgte 2015 die überarbeitete Version. Die dritte Ausgabe der IC3D wurde im Februar 2024 veröffentlicht und ist frei zugänglich. Die neueste Auflage soll als Nachschlagewerk im klinischen Alltag dienen und die Diagnose von HD erleichtern. Dieser Artikel bietet einen Überblick über die Diagnose- und Behandlungsprinzipien der HD und stellt die IC3D und deren Veränderungen im Laufe der Zeit vor.