19 research outputs found
Pathogenic and low-frequency variants in children with central precocious puberty
Background: Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were investigated in patients with CPP. Methods: Fifty-four index girls and two index boys with CPP were first tested by Sanger sequencing for the MKRN3 gene. All children found negative (n = 44) for the MKRN3 gene were further investigated by whole exome sequencing (WES). In the latter analysis, the status of variants in genes known to be related with pubertal timing was compared with an in-house Cypriot control cohort (n = 43). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes was designed. Results: Three previously described pathogenic MKRN3 variants located in the coding region of the gene were identified in 12 index girls with CPP. The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively found among the Cypriot CPP cohort, indicating a founder effect phenomenon. Seven other CPP girls harbored rare likely pathogenic upstream variants in the MKRN3. Among the 44 CPP patients submitted to WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1 variants in six girls, and two rare MAGEL2 variants in five girls. Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R gene appeared to be less frequent in the cohort of patients with CPP. Conclusion: The results of the present study confirm the importance of the MKRN3-imprinted gene in genetics of CPP and its key role in pubertal timing. Overall, the results of the present study have emphasized the importance of an approach that aligns genetics and clinical aspects, which is necessary for the management and treatment of CPP
Evaluation of myocardial iron accumulation in b-thalassaemia with magnetic resonance imaging (MRI): clinical correlations
An Improved Fuzzy C-Means Algorithm for the Implementation of Demand Side Management Measures
Load profiling refers to a procedure that leads to the formulation of daily load curves and consumer classes regarding the similarity of the curve shapes. This procedure incorporates a set of unsupervised machine learning algorithms. While many crisp clustering algorithms have been proposed for grouping load curves into clusters, only one soft clustering algorithm is utilized for the aforementioned purpose, namely the Fuzzy C-Means (FCM) algorithm. Since the benefits of soft clustering are demonstrated in a variety of applications, the potential of introducing a novel modification of the FCM in the electricity consumer clustering process is examined. Additionally, this paper proposes a novel Demand Side Management (DSM) strategy for load management of consumers that are eligible for the implementation of Real-Time Pricing (RTP) schemes. The DSM strategy is formulated as a constrained optimization problem that can be easily solved and therefore, making it a useful tool for retailers’ decision-making framework in competitive electricity markets
Effectiveness of artificial pancreas in children and adolescents with Type 1 Diabetes Mellitus: a systematic review and meta-analysis
This study aims to systematically review the current literature and conduct a meta-analysis investigating the efficacy of artificial pancreas in the glycemic control of children, adolescents and young adults with T1DM
Cortisol Levels in Glucagon Stimulation Test in Children Assessed for Short Stature: Clinical and Laboratorial Correlations
Subcutaneous Fat Necrosis and Hypercalcemia with Nephrocalcinosis in Infancy: Case Report and Review of the Literature
Subcutaneous fat necrosis is an uncommon benign panniculitis affecting more commonly full-term newborns. It has been associated with birth asphyxia and meconium aspiration, as well as therapeutic hypothermia. Although the prognosis is generally favorable, complications such as hypercalcemia, thrombocytopenia, hypoglycemia and hypertriglyceridemia may complicate its course. The most serious complication is hypercalcemia that may reach life threatening levels and can be associated with nephrocalcinosis. We thereby describe a case of subcutaneous fat necrosis after therapeutic hypothermia, which presented with late-onset refractory severe hypercalcemia and persistent nephrocalcinosis during the follow up of the patient. Due to the risk of the development of chronic kidney disease, we highlight the importance of careful monitoring of hypercalcemia and review the literature of subcutaneous fat necrosis related to nephrocalcinosis
Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature
Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs’ biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to β-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity
Increased osteoclastic activity as shown by increased sRANK-L/OPG ratio in boys with hemophilia
Coronavirus lockdown effect on type 1 diabetes management οn children wearing insulin pump equipped with continuous glucose monitoring system
Pathogenic and Low-Frequency Variants in Children With Central Precocious Puberty
Background
Central precocious puberty (CPP) due to premature activation of GnRH
secretion results in early epiphyseal fusion and to a significant
compromise in the achieved final adult height. Currently, few genetic
determinants of children with CPP have been described. In this
translational study, rare sequence variants in MKRN3, DLK1, KISS1, and
KISS1R genes were investigated in patients with CPP
Methods
Fifty-four index girls and two index boys with CPP were first tested by
Sanger sequencing for the MKRN3 gene. All children found negative (n =
44) for the MKRN3 gene were further investigated by whole exome
sequencing (WES). In the latter analysis, the status of variants in
genes known to be related with pubertal timing was compared with an
in-house Cypriot control cohort (n = 43). The identified rare variants
were initially examined by in silico computational algorithms and
confirmed by Sanger sequencing. Additionally, a genetic network for the
MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk
between MKRN3 and other genes was designed.
Results
Three previously described pathogenic MKRN3 variants located in the
coding region of the gene were identified in 12 index girls with CPP.
The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively
found among the Cypriot CPP cohort, indicating a founder effect
phenomenon. Seven other CPP girls harbored rare likely pathogenic
upstream variants in the MKRN3. Among the 44 CPP patients submitted to
WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1
variants in six girls, and two rare MAGEL2 variants in five girls.
Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R
gene appeared to be less frequent in the cohort of patients with CPP.
Conclusion
The results of the present study confirm the importance of the
MKRN3-imprinted gene in genetics of CPP and its key role in pubertal
timing. Overall, the results of the present study have emphasized the
importance of an approach that aligns genetics and clinical aspects,
which is necessary for the management and treatment of CPP