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Human Genome Variation May 2024Germline loss-of-function mutations in USP9X have been reported to cause a wide spectrum of congenital anomalies. Here, we report a Japanese girl with a novel...
Germline loss-of-function mutations in USP9X have been reported to cause a wide spectrum of congenital anomalies. Here, we report a Japanese girl with a novel heterozygous nonsense mutation in USP9X who exhibited intellectual disability with characteristic craniofacial abnormalities, including hypotelorism, brachycephaly, hypodontia, micrognathia, severe dental crowding, and an isolated submucous cleft palate. Our findings provide further evidence that disruptions in USP9X contribute to a broad range of congenital craniofacial abnormalities.
PubMed: 38755172
DOI: 10.1038/s41439-024-00277-w -
Anais Da Academia Brasileira de Ciencias 2024Brachycephalic breeds of dogs, most of which show signs of the brachycephalic syndrome may have greater parasympathetic stimulation than other breeds, leading to higher...
Brachycephalic breeds of dogs, most of which show signs of the brachycephalic syndrome may have greater parasympathetic stimulation than other breeds, leading to higher values of heart rate variability and vagal tone index. The aim of this study was to establish a computerized electrocardiographic study and an assessment of the vagus sympathetic balance through heart rate variability and vagal tone index of five brachycephalic breeds compared to mesocephalic dogs. Sixty dogs were used, divided into groups made up of Boxers, English Bulldogs, French Bulldogs, Pugs, Shih-Tzu and no defined breed mesocephalic dogs. Statistical analysis was carried out using the Shapiro-Wilk test, Kruskal-Wallis and Dunn's test or ANOVA and Bonferroni (p<0.05). In the evaluation of vagal sympathetic balance among all the dogs, there was a negative correlation between heart rate and HRV 10RR (r = - 0.7678; p < 0.0001), HRV 20RR (r = - 0.8548, p < 0.0001) and VVTI (r = - 0.2770; p = 0.0321). It can therefore be concluded that the dog's breed and morphology did not alter its electrocardiographic parameters or heart rate variability. The vagal tone index, which in other studies differed in brachycephalic dogs, showed no difference when compared separately in brachycephalic breeds.
Topics: Animals; Dogs; Heart Rate; Vagus Nerve; Electrocardiography; Male; Female; Craniosynostoses
PubMed: 38747800
DOI: 10.1590/0001-3765202420231250 -
JAMA Network Open Apr 2024Several studies have reported a higher incidence of neurodevelopmental delays and cognitive deficits in patients with single-suture craniosynostosis; however, there are...
IMPORTANCE
Several studies have reported a higher incidence of neurodevelopmental delays and cognitive deficits in patients with single-suture craniosynostosis; however, there are few studies examining the associations of repair type with cognitive outcomes.
OBJECTIVE
To measure differences in neuropsychological outcomes between school-age children who were treated for sagittal craniosynostosis and unaffected controls and explore differences in cognitive function among children with sagittal craniosynostosis who were previously treated with either endoscopic strip craniectomy or open calvarial vault surgery.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was performed between 2018 and 2022. Eligible participants included patients aged 5 to 17 years who had previously been seen as infants or toddlers (<3 years) at 1 of 3 surgical centers for craniosynostosis repair with either endoscopic surgery or open calvarial vault surgery. A separate cohort of unaffected controls were included for comparison. Data analysis was conducted from November 2023 to February 2024.
EXPOSURES
Open calvarial vault surgery or endoscopic repair for single-suture craniosynostosis.
MAIN OUTCOMES AND MEASURES
The primary outcome was the Differential Ability Scales-II (DAS-II) General Conceptual Ability (GCA) score, an index for overall intellectual ability. Secondary outcomes included DAS-II subscale scores (Verbal Ability, Nonverbal Reasoning, Spatial Ability, Working Memory, and Processing Speed), and Patient-Reported Outcomes Measurement Information System (PROMIS) cognitive function scores.
RESULTS
A total of 81 patients with sagittal craniosynostosis (59 male [73%]; 22 female [27%]) and 141 controls (81 male [57%]; 60 female [43%]) were included. Of the 81 participants with sagittal craniosynostosis, 46 underwent endoscopic repair and 35 underwent open repair. Median (range) age at time of follow-up assessment was 7.7 (5.0-14.8) years for children with sagittal craniosynostosis and median age at assessment was 8.5 (7.7-10.5) years for controls. After controlling for age at assessment, sex, and socioeconomic status, there was no statistically significant or clinically meaningful difference in GCA scores between children who underwent endoscopic repair (adjusted mean score, 100; 95% CI, 96-104) and open repair (adjusted mean score, 103; 95% CI, 98-108) (P > .99). We found no significant difference in PROMIS scores between repair types (median [range] for endoscopic repair 54 [31-68] vs median [range] for open repair 50 [32-63]; P = .14). When comparing the treatment groups with the unaffected controls, differences in subscale scores for GCA and working memory were observed but were within normal range.
CONCLUSIONS AND RELEVANCE
In this cohort study, there were no statistically or clinically significant differences in cognitive outcomes among school-age children by and type of surgical procedure used to repair nonsyndromic sagittal craniosynostosis. These findings suggest primary care clinicians should be educated about different options for craniosynostosis surgery to ensure early referral of these patients so that all treatment options remain viable.
Topics: Humans; Craniosynostoses; Male; Female; Child; Child, Preschool; Endoscopy; Adolescent; Cognition; Cohort Studies; Craniotomy; Treatment Outcome; Skull; Neuropsychological Tests
PubMed: 38683606
DOI: 10.1001/jamanetworkopen.2024.8762 -
Genes Mar 2024The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated... (Review)
Review
The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated trafficking of integral membrane proteins. Mutations affecting all subunits of the AP-4 complex have been linked to autosomal-recessive cerebral palsy and a complex hereditary spastic paraparesis (HSP) phenotype. Our report details the case of a 14-year-old boy born to consanguineous parents, presenting psychomotor delay, severe intellectual disability, microcephaly, and trigonocephaly. Despite a history of febrile seizures, subsequent years were devoid of seizures, with normal EEG. Exome sequencing revealed pathogenic variants in both the and genes. Significantly, the patient exhibited features associated with mutations, including distinctive traits such as cranial malformations. The gene variant, linked to craniosynostosis, likely contributes to the observed trigonocephaly. This case represents the initial documentation of a concurrent mutation in the and genes, underscoring the critical role of exome analysis in unraveling complex phenotypes. Understanding these complex genotypes offers valuable insights into broader syndromic conditions, facilitating comprehensive patient management.
Topics: Humans; Male; Adolescent; Phenotype; Mutation; Peptide Termination Factors; Adaptor Protein Complex 4; Intellectual Disability; Exome Sequencing; Microcephaly; Craniosynostoses; Repressor Proteins
PubMed: 38674371
DOI: 10.3390/genes15040436 -
Animals : An Open Access Journal From... Mar 2024Fashions in the appearance of purebred dogs and cats are encouraged by celebrity culture, social media, and online impulse buying. The popularity of characteristics...
Fashions in the appearance of purebred dogs and cats are encouraged by celebrity culture, social media, and online impulse buying. The popularity of characteristics perceived as cute, quirky, and anthropomorphic has driven increasingly exaggerated breed features appealing to aesthetics rather than health. 'Hypertypes' of some breeds have emerged that take a breed's distinctive appearance to extremes beyond the intended interpretation of breed standards. This has severe, direct and indirect health and welfare consequences. Extreme conformations are associated with chronic health conditions including brachycephalic obstructive airway disorder, ocular, dental, skin, and musculoskeletal disorders. Puppy and kitten farms and illegal traders that meet the demand for hypertypes are associated with poor husbandry that neglects the physical, behavioral, and mental health of parents and offspring. A multidimensional approach involving collaboration between breeders, geneticists, owners, veterinarians, kennel clubs, cat fanciers' associations, animal charities, the academic and research communities, commercial enterprises, and governments is needed to safeguard breeds and tackle these challenges. There are many ongoing initiatives by national kennel clubs and global partnerships to educate pet owners and support responsible pet ownership and sustainable breeding. The resounding message is that health, temperament, and well-being must be prioritized over appearance.
PubMed: 38612242
DOI: 10.3390/ani14071003 -
Scientific Reports Apr 2024Craniosynostosis (CS) is a major birth defect resulting from premature fusion of cranial sutures. Nonsyndromic CS occurs more frequently than syndromic CS, with sagittal...
Craniosynostosis (CS) is a major birth defect resulting from premature fusion of cranial sutures. Nonsyndromic CS occurs more frequently than syndromic CS, with sagittal nonsyndromic craniosynostosis (sNCS) presenting as the most common CS phenotype. Previous genome-wide association and targeted sequencing analyses of sNCS have identified multiple associated loci, with the strongest association on chromosome 20. Herein, we report the first whole-genome sequencing study of sNCS using 63 proband-parent trios. Sequencing data for these trios were analyzed using the transmission disequilibrium test (TDT) and rare variant TDT (rvTDT) to identify high-risk rare gene variants. Sequencing data were also examined for copy number variants (CNVs) and de novo variants. TDT analysis identified a highly significant locus at 20p12.3, localized to the intergenic region between BMP2 and the noncoding RNA gene LINC01428. Three variants (rs6054763, rs6054764, rs932517) were identified as potential causal variants due to their probability of being transcription factor binding sites, deleterious combined annotation dependent depletion scores, and high minor allele enrichment in probands. Morphometric analysis of cranial vault shape in an unaffected cohort validated the effect of these three single nucleotide variants (SNVs) on dolichocephaly. No genome-wide significant rare variants, de novo loci, or CNVs were identified. Future efforts to identify risk variants for sNCS should include sequencing of larger and more diverse population samples and increased omics analyses, such as RNA-seq and ATAC-seq.
Topics: Humans; Alleles; Bone Morphogenetic Protein 2; Craniosynostoses; DNA, Intergenic; Genome-Wide Association Study; Whole Genome Sequencing; RNA, Long Noncoding
PubMed: 38609424
DOI: 10.1038/s41598-024-58343-w -
Journal of Veterinary Internal Medicine 2024Aerophagia (ingestion of air), is a functional aerodigestive disorder in people. Criteria for diagnosis of aerophagia in dogs are >1/3 of bolus volume containing air or...
BACKGROUND
Aerophagia (ingestion of air), is a functional aerodigestive disorder in people. Criteria for diagnosis of aerophagia in dogs are >1/3 of bolus volume containing air or ingested air resulting in gastric distention (>1/3 of end gastric volume). Aerophagia is highlighted during eating and drinking. Videofluoroscopic swallow studies (VFSS) document aerophagia in dogs, but the incidence, clinical signs (CS), and associated disorders are unknown.
OBJECTIVES
Identify the incidence of aerophagia, compare CS between dogs with and without aerophagia, and identify associated and predisposing disorders using VFSS.
ANIMALS
A total of 120 client-owned dogs.
METHODS
Sequential VFSS and associated medical records from dogs presenting to veterinary teaching hospitals at Auburn University and the University of Missouri were retrospectively reviewed. Statistical comparisons were made using Mann-Whitney and chi-squared tests, odds ratios (OR), and multiple logistic regression (P < .05).
RESULTS
The incidence (95% confidence interval [CI]) of aerophagia was 40% (31.7-48.9). Dogs with mixed CS (gastrointestinal [GI] and respiratory; P < .001, 58.3%) were more likely to have aerophagia than dogs with exclusively respiratory CS (25%). Aerophagia was significantly more common in brachycephalic dogs (P = .01; 45.8% vs 13.8%), dogs with nonbrachycephalic upper airway obstruction (P < .001; 33.3% vs 4.1%), pathologic penetration and aspiration (P-A) scores (P = .04; 41.6% vs 23.6%), and gagging (P < .001; 25% vs 11.7%). Mixed CS (P = .01), brachycephaly (P < .001), and upper airway obstruction (P < .001) were independent predictors of aerophagia.
CONCLUSIONS AND CLINICAL IMPORTANCE
Aerophagia was common, particularly in dogs with mixed CS. Brachycephalic dogs and dogs with upper airway obstruction are predisposed. Aspiration risk was high, emphasizing overlapping upper aerodigestive pathways.
Topics: Animals; Dogs; Dog Diseases; Female; Male; Retrospective Studies; Fluoroscopy; Incidence; Aerophagy; Video Recording; Deglutition
PubMed: 38561963
DOI: 10.1111/jvim.17054 -
Genes Mar 2024Many coat color, behavioral and morphological traits are specific and fixed across cat breeds, with several variants influencing these traits being common among...
Many coat color, behavioral and morphological traits are specific and fixed across cat breeds, with several variants influencing these traits being common among different breeds. In the domestic cat, rexoid mutations have been documented in several breeds. In the Cornish Rex, four bp deletion in the gene has been found to cause a frame shift and a premature stop codon. In addition to the rexoid coat, Cornish Rex cats also have a characteristic head, ear shape and body type. Analysis of the selection signatures in the Cornish Rex genome revealed several regions that are under selective pressure. One of these is located in CFA B4, in the region where the gene is located. The gene in Burmese cats disrupts the cranial morphogenesis and causes brachycephaly in the heterozygous state. In our study, we confirmed the presence of a deletion in in 20 Cornish Rex and in four F1 hybrids between Cornish Rex and domestic cat. However, we did not confirm the presence of the deletion in in Cornish Rex cats. Genome-wide selection signature analysis was performed using ROH islands and integrated haplotype score (iHS) statistics based on publicly available SNP array data of 11 Cornish Rex cats. The selection signatures were detected on chromosomes A1, A3, C2, B1, B4 and D1.
Topics: Cats; Animals; Phenotype; Genome; Haplotypes; Mutation; Heterozygote
PubMed: 38540427
DOI: 10.3390/genes15030368 -
Iranian Journal of Allergy, Asthma, and... Feb 2024Sanjad Sakati Syndrome (SSS) is categorized as a neuroendocrine-related disease due to disorders of the nervous and hormonal systems. Since hormonal changes in these...
Sanjad Sakati Syndrome (SSS) is categorized as a neuroendocrine-related disease due to disorders of the nervous and hormonal systems. Since hormonal changes in these patients may affect the nature and function of the immune system. Thus, in this study, cell count and phagocytotic function of neutrophils were evaluated which may be influenced by changes in the hormonal rate and growth factors. In this study, the neutrophil count value and the oxidative burst were evaluated in six patients diagnosed with SSS and six healthy individuals. There was a significant reduction in the neutrophil count observed in SSS patients compared to healthy controls (37.41±7.93 percent vs. 66.5±6.8 percent). However, there was no significant difference in neutrophil oxidative index between patients with SSS and control subjects (172.33±55.08 vs. 217.00±77.38). We concluded that in patients with SSS, the phagocytic activity of neutrophils was not affected by hormonal changes, while the number of neutrophils and neutrophil-to-lymphocyte ratio (NLR) index were decreased.
Topics: Humans; Neutrophils; Respiratory Burst; Intellectual Disability; Leukocyte Count; Lymphocyte Count; Abnormalities, Multiple; Growth Disorders; Acrocephalosyndactylia; Osteochondrodysplasias; Hypoparathyroidism; Seizures
PubMed: 38485906
DOI: 10.18502/ijaai.v23i1.14959