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Frontiers in Endocrinology 2023Spinal kinematics/motion are reported to be altered in adolescents and adults with essential obesity, while no information is available in patients with Prader-Willi...
INTRODUCTION
Spinal kinematics/motion are reported to be altered in adolescents and adults with essential obesity, while no information is available in patients with Prader-Willi syndrome so far. The aim of this study was to examine cross-sectionally the characteristics of spinal postures and mobility in 34 patients with PWS, in 35 age- and sex-matched adults with essential obesity, and in 37 normal-weight individuals.
METHODS
Spinal posture and mobility were assessed using a radiation-free back scan, the Idiag M360 (Idiag, Fehraltorf, Switzerland). Differences in spinal posture and mobility between the three groups were determined using a two-way analysis of variance.
RESULTS
Adults with Prader-Willi syndrome had greater thoracic kyphosis [difference between groups (Δ) = 9.6, 95% CI 3.3 to 15.6, p = 0.001], less lumbar lordosis (Δ = -6.5, 95% CI -12.7 to -0.3, p = 0.03) as well as smaller lumbar and hip mobility than those with normal weight.
DISCUSSION
Although the characteristics of the spine in patients with Prader-Will syndrome appear to be similar to that found in subjects with essential obesity, Prader-Willi syndrome was found to influence lumbar movements more than thoracic mobility. These results provide relevant information about the characteristics of the spine in adults with Prader-Willi syndrome to be taken into careful consideration in the management of spinal conditions. These findings also highlight the importance of considering the musculoskeletal assessment of spinal postures and approaches targeting spinal and hip flexibility in adults with Prader-Willi syndrome.
Topics: Adolescent; Humans; Adult; Prader-Willi Syndrome; Obesity; Posture; Switzerland
PubMed: 37800136
DOI: 10.3389/fendo.2023.1235030 -
IJU Case Reports Jul 2023Prader-Willi syndrome is a congenital disorder that occurs in one in 10 000-30 000 children and is characterized by obesity, short stature, and intellectual disability.
INTRODUCTION
Prader-Willi syndrome is a congenital disorder that occurs in one in 10 000-30 000 children and is characterized by obesity, short stature, and intellectual disability.
CASE PRESENTATION
A 24-year-old male patient with Prader-Willi syndrome presented with an enlarged adrenal tumor. Computed tomography detected a well-defined mass. Magnetic resonance imaging revealed an increased signal intensity predominantly in fatty areas, suggesting adrenal myelolipoma. Laparoscopic left adrenalectomy was performed. Postoperatively, the patient developed mild pulmonary atelectasis, myelolipoma was confirmed by histopathology, and there was no recurrence at approximately 2 years postoperatively.
CONCLUSION
This is the first report of Prader-Willi syndrome complicated with adrenal myelolipoma, which was removed laparoscopically.
PubMed: 37405031
DOI: 10.1002/iju5.12595 -
Acta Neuropathologica Mar 2024Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder of genetic etiology, characterized by paternal deletion of genes located at chromosome 15 in 70% of...
Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder of genetic etiology, characterized by paternal deletion of genes located at chromosome 15 in 70% of cases. Two distinct genetic subtypes of PWS deletions are characterized, where type I (PWS T1) carries four extra haploinsufficient genes compared to type II (PWS T2). PWS T1 individuals display more pronounced physiological and cognitive abnormalities than PWS T2, yet the exact neuropathological mechanisms behind these differences remain unclear. Our study employed postmortem hypothalamic tissues from PWS T1 and T2 individuals, conducting transcriptomic analyses and cell-specific protein profiling in white matter, neurons, and glial cells to unravel the cellular and molecular basis of phenotypic severity in PWS sub-genotypes. In PWS T1, key pathways for cell structure, integrity, and neuronal communication are notably diminished, while glymphatic system activity is heightened compared to PWS T2. The microglial defect in PWS T1 appears to stem from gene haploinsufficiency, as global and myeloid-specific Cyfip1 haploinsufficiency in murine models demonstrated. Our findings emphasize microglial phagolysosome dysfunction and altered neural communication as crucial contributors to the severity of PWS T1's phenotype.
Topics: Humans; Mice; Animals; Prader-Willi Syndrome; Microglia; Carrier Proteins; Phenotype; Phagosomes; Adaptor Proteins, Signal Transducing
PubMed: 38556574
DOI: 10.1007/s00401-024-02714-0 -
Neuroradiology Jan 2024Prader-Willi syndrome (PWS) suffers from brain functional reorganization and developmental delays during childhood, but the underlying neurodevelopmental mechanism is...
PURPOSE
Prader-Willi syndrome (PWS) suffers from brain functional reorganization and developmental delays during childhood, but the underlying neurodevelopmental mechanism is unclear. This paper aims to investigate the intra- and internetwork functional connectivity (FC) changes, and their relationships with developmental delays in PWS children.
METHODS
Resting-state functional magnetic resonance imaging datasets of PWS children and healthy controls (HCs) were acquired. Independent component analysis was used to acquire core resting-state networks (RSNs). The intra- and internetwork FC patterns were then investigated.
RESULTS
In terms of intranetwork FC, children with PWS had lower FC in the dorsal attention network, the auditory network, the medial visual network (VN) and the sensorimotor network (SMN) than HCs (FWE-corrected, p < 0.05). In terms of internetwork FC, PWS children had decreased FC between the following pairs of regions: posterior default mode network (DMN) and anterior DMN; posterior DMN and SMN; SMN and posterior VN and salience network and medial VN (FDR-corrected, p < 0.05). Partial correlation analyses revealed that the intranetwork FC patterns were positively correlated with developmental quotients in PWS children, while the internetwork FC patterns were completely opposite (p < 0.05). Intranetwork FC patterns showed an area under the receiver operating characteristic curve of 0.947, with a sensitivity of 96.15% and a specificity of 81.25% for differentiating between PWS and HCs.
CONCLUSION
Impaired intra- and internetwork FC patterns in PWS children are associated with developmental delays, which may result from neural pathway dysfunctions. Intranetwork FC reorganization patterns can discriminate PWS children from HCs.
REGISTRATION NUMBER ON THE CHINESE CLINICAL TRAIL REGISTRY
ChiCTR2100046551.
Topics: Child; Humans; Prader-Willi Syndrome; Brain Mapping; Magnetic Resonance Imaging; Nerve Net; Brain
PubMed: 38001311
DOI: 10.1007/s00234-023-03259-x -
Frontiers in Medicine 2023Prader-Willi syndrome (PWS) is a rare disease caused by a lack of expression of inherited imprinted genes in the paternally derived Prader-Willi critical region on...
Register-based and genetic studies of Prader-Willi syndrome show a high frequency of gonadal tumors and a possible mechanism for tumorigenesis through imprinting relaxation.
Prader-Willi syndrome (PWS) is a rare disease caused by a lack of expression of inherited imprinted genes in the paternally derived Prader-Willi critical region on chromosome 15q11.2-q13. It is characterized by poor feeding and hypotonia in infancy, intellectual disability, behavioral abnormalities, dysmorphic features, short stature, obesity, and hypogonadism. PWS is not a known cancer predisposition syndrome, but previous investigations regarding the prevalence of cancer in these patients suggest an increased risk of developing specific cancer types such as myeloid leukemia and testicular cancer. We present the results from a Swedish national population-based cohort study of 360 individuals with PWS and 18,000 matched comparisons. The overall frequency of cancer was not increased in our PWS cohort, but we found a high frequency of pediatric cancers. We also performed whole-genome sequencing of blood- and tumor-derived DNAs from a unilateral dysgerminoma in a 13-year-old girl with PWS who also developed bilateral ovarian sex cord tumors with annular tubules. In germline analysis, there were no additional findings apart from the 15q11.2-q13 deletion of the paternal allele, while a pathogenic activating mutation was identified in the tumor. Additionally, methylation-specific multiplex ligation-dependent probe amplification revealed reduced methylation at the PWS locus in the dysgerminoma but not in the blood. In conclusion, our register-based study suggests an increased risk of cancer at a young age, especially testicular and ovarian tumors. We found no evidence of a general increase in cancer risk in patients with PWS. However, given our limited observational time, further studies with longer follow-up times are needed to clarify the lifetime cancer risk in PWS. We have also described the second case of locus-specific loss-of-imprinting in a germ cell tumor in PWS, suggesting a possible mechanism of carcinogenesis.
PubMed: 37575996
DOI: 10.3389/fmed.2023.1172565 -
Case Reports in Genetics 2023Loss of expression of paternally imprinted genes in the 15q11.2-q13 chromosomal region leads to the neurodevelopmental disorder Prader-Willi Syndrome (PWS). The PWS...
Loss of expression of paternally imprinted genes in the 15q11.2-q13 chromosomal region leads to the neurodevelopmental disorder Prader-Willi Syndrome (PWS). The PWS critical region contains four paternally expressed protein-coding genes along with small nucleolar RNA (snoRNA) genes under the control of the promoter, including the snoRNA gene cluster that is implicated in the PWS disease etiology. A 5-7 Mb deletion, maternal uniparental disomy, or an imprinting defect of chromosome 15q affect multiple genes in the PWS critical region, causing PWS. However, the individual contributions of these genes to the PWS phenotype remain elusive. Reports of smaller, atypical deletions may refine the boundaries of the PWS critical region or suggest additional disease-causing mechanisms. We describe an adult female with a classic PWS phenotype due to a 78 kb microdeletion that includes only exons 2 and 3 of with apparently preserved expression of .
PubMed: 37736297
DOI: 10.1155/2023/4225092 -
BMJ Paediatrics Open May 2024
PubMed: 38719566
DOI: 10.1136/bmjpo-2019-000630corr1 -
Frontiers in Neuroscience 2024
PubMed: 38476870
DOI: 10.3389/fnins.2024.1370030 -
International Journal of Molecular... Sep 2023Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the... (Review)
Review
Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the (), which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR isoform, which lacks exon 3 has recently been related to longevity; individuals carrying this isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the wild type (WT) isoform (flGHR). Further, studies performed in patients with acromegaly, Prader-Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR isoform may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.
PubMed: 37762211
DOI: 10.3390/ijms241813908 -
BMC Bioinformatics Feb 2024DNA methylation is one of the most stable and well-characterized epigenetic alterations in humans. Accordingly, it has already found clinical utility as a molecular...
BACKGROUND
DNA methylation is one of the most stable and well-characterized epigenetic alterations in humans. Accordingly, it has already found clinical utility as a molecular biomarker in a variety of disease contexts. Existing methods for clinical diagnosis of methylation-related disorders focus on outlier detection in a small number of CpG sites using standardized cutoffs which differentiate healthy from abnormal methylation levels. The standardized cutoff values used in these methods do not take into account methylation patterns which are known to differ between the sexes and with age.
RESULTS
Here we profile genome-wide DNA methylation from blood samples drawn from within a cohort composed of healthy controls of different age and sex alongside patients with Prader-Willi syndrome (PWS), Beckwith-Wiedemann syndrome, Fragile-X syndrome, Angelman syndrome, and Silver-Russell syndrome. We propose a Generalized Additive Model to perform age and sex adjusted outlier analysis of around 700,000 CpG sites throughout the human genome. Utilizing z-scores among the cohort for each site, we deployed an ensemble based machine learning pipeline and achieved a combined prediction accuracy of 0.96 (Binomial 95% Confidence Interval 0.868[Formula: see text]0.995).
CONCLUSION
We demonstrate a method for age and sex adjusted outlier detection of differentially methylated loci based on a large cohort of healthy individuals. We present a custom machine learning pipeline utilizing this outlier analysis to classify samples for potential methylation associated congenital disorders. These methods are able to achieve high accuracy when used with machine learning methods to classify abnormal methylation patterns.
Topics: Humans; Genomic Imprinting; DNA Methylation; Beckwith-Wiedemann Syndrome; Silver-Russell Syndrome; Supervised Machine Learning
PubMed: 38347515
DOI: 10.1186/s12859-024-05673-1