Dent Disease in Chinese Children and Findings from Heterozygous Mothers: Phenotypic Heterogeneity, Fetal Growth, and 10 Novel Mutations.

Par Antoine Blanchard et Mélodie Faury pour le collectif Révoluscience Billet publié simultanément sur Sciences et Démocratie et Knowtex Blog Les "lieux" des réactions Plusieurs dispositifs avaient été mis en place pour recueillir les réactions des lecteurs, d'abord sur le blog du manifeste où les commentaires étaient possibles sous chaque proposition, puis sur un site de travail collaboratif permettant d’en annoter le texte, paragraphe par paragraphe. On alliait ainsi critique d'un côté et..

Dent Disease in Chinese Children and Findings from Heterozygous Mothers: Phenotypic Heterogeneity, Fetal Growth, and 10 Novel Mutations.

OBJECTIVE: To characterize the phenotypes of Dent disease in Chinese children and their heterozygous mothers and to establish genetic diagnoses. STUDY DESIGN: Using a modified protocol, we screened 1288 individuals with proteinuria. A diagnosis of Dent disease was established in 19 boys from 16 families by the presence of loss of function/deleterious mutations in CLCN5 or OCRL1. We also analyzed 16 available patients' mothers and examined their pregnancy records. RESULTS: We detected 14 loss of function/deleterious mutations of CLCN5 in 15 boys and 2 mutations of OCRL1 in 4 boys. Of the patients, 16 of 19 had been wrongly diagnosed with other diseases and 11 of 19 had incorrect or unnecessary treatment. None of the patients, but 6 of 14 mothers, had nephrocalcinosis or nephrolithiasis at diagnosis. Of the patients, 8 of 14 with Dent disease 1 were large for gestational age (>90th percentile); 8 of 15 (53.3%) had rickets. We also present predicted structural changes for 4 mutant proteins. CONCLUSIONS: Pediatric Dent disease often is misdiagnosed; genetic testing achieves a correct diagnosis. Nephrocalcinosis or nephrolithiasis may not be sensitive diagnostic criteria. We identified 10 novel mutations in CLCN5 and OCRL1. The possibility that altered CLCN5 function could affect fetal growth and a possible link between a high rate of rickets and low calcium intake are discussed

The Effect of Metabolic Syndrome and Its Individual Components on Renal Function: A Meta-Analysis

Background: Observational studies have reported inconsistent findings in the relationship between metabolic syndrome (MetS), its components, and loss of renal function, mainly including eGFR decline, new-onset CKD, and ESRD. This meta-analysis was performed to investigate their potential associations. Methods: PubMed and EMBASE were systematically searched from their inception to 21 July 2022. Observational cohort studies in English assessing the risk of renal dysfunction in individuals with MetS were identified. Risk estimates and their 95% confidence intervals (CIs) were extracted and pooled using the random-effects approach. Results: A total of 32 studies with 413,621 participants were included in the meta-analysis. MetS contributed to higher risks of renal dysfunction (RR = 1.50, 95% CI = 1.39–1.61) and, specifically, rapid decline in eGFR (RR 1.31, 95% CI 1.13–1.51), new-onset CKD (RR 1.47, 95% CI 1.37–1.58), as well as ESRD (RR 1.55, 95% CI 1.08–2.22). Moreover, all individual components of MetS were significantly associated with renal dysfunction, while elevated BP conveyed the highest risk (RR = 1.37, 95% CI = 1.29–1.46), impaired fasting glucose with the lowest and diabetic-dependent risk (RR = 1.20, 95% CI = 1.09–1.33). Conclusions: Individuals with MetS and its components are at higher risk of renal dysfunction

The phenomena of balanced effect between α-globin gene and of β-globin gene

Abstract Background Thalassemias (TM) are the most common autosomal recessive disorders in Southeast Asian countries. Both α- and β-thalassemia lead to a decrease or absence of globin chains. The most serious of the thalassemia syndromes is thalassemia major which is characterized by a transfusion dependent anemia and subsequent iron overload caused by repeated blood transfusions. It is preventive by genotyping the parents. A better understanding of the laboratory data will help provide an accurate diagnosis of thalassemia major, and prevention and controlling programs in routine laboratories. Case presentation The patient was a one-year-old boy born to non-consanguineous parents. He was referred to our outpatient clinic for hemolytic anemia after a cold. Hematological investigations revealed severe anemia (Hb57 g/dL). The red cells displayed microcytosis, hypochromia and misshapen erythrocytes (MCV48.8 fL, MCH15.7 pg). Capillary electrophoresis (CE) electropherogram revealed normal level of HbA2 (3.2%) and elevated HbF (35.1%). The patient was diagnosed with β-TM, based on severe microcytosis, hypochromia, normal Hb A2 and high Hb F level but no Hb H inclusion at the first visit. Later our molecular analysis revealed compound heterozygosity for codons 41–42 (-TTCT) (HBB: c.126_129delCTTT, β0) and IVS-II-654 (C > T) (HBB: c.316-197C > T, β+) mutation and deletional Hb H (−-SEA/−α3.7). Thus, a combination of Hb H disease and a compound heterozygosity of β+/β0-thalassemia (β+/β0-thal) was finally diagnosed. Conclusions Genotype-phenotype analysis shows that heterozygous mutations in the β-globin gene could affect not only hematological parameters, but also elevate HbA2 levels. These effects could be ameliorated by the coinheritance of Hb H disease, which may be explained by the phenomena of the α-globin gene and of the β-globin gene balanced effect

EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis

International audienceMultiple osteochondromas (MO), the most common type of benign bone tumor, is an autosomal dominant skeletal disorder characterized by multiple cartilage-capped bony protuberances. In most cases, EXT1 and EXT2 , which encode glycosyltransferases involved in the biosynthesis of heparan sulfate, are the genes responsible. Here we describe the clinical, phenotypic and genetic characterization of MO in 22 unrelated Chinese families involving a total of 60 patients. Variant detection was performed by means of a battery of different techniques including Sanger sequencing and whole-exome sequencing (WES). The pathogenicity of the missense and splicing variants was explored by means of in silico prediction algorithms. Sixteen unique pathogenic variants, including 10 in the EXT1 gene and 6 in the EXT2 gene, were identified in 18 (82%) of the 22 families. Fourteen (88%) of the 16 variants were predicted to give rise to truncated proteins whereas the remaining two were missense. Seven variants were newly described here, further expanding the spectrum of MO-causing variants in the EXT1 and EXT2 genes. More importantly, the identification of causative variants allowed us to provide genetic counseling to 8 MO patients in terms either of preimplantation genetic testing (PGT) or prenatal diagnosis, thereby preventing the reoccurrence of MO in the corresponding families. This study is the first to report the successful implementation of PGT in MO families and describes the largest number of subjects undergoing prenatal diagnosis to date

ZMYND10, an epigenetically regulated tumor suppressor, exerts tumor-suppressive functions via miR145-5p/NEDD9 axis in breast cancer (vol 11, 184, 2019)

10.1186/s13148-022-01256-0CLINICAL EPIGENETICS14

ZMYND10, an epigenetically regulated tumor suppressor, exerts tumor-suppressive functions via miR145-5p/NEDD9 axis in breast cancer

10.1186/s13148-019-0785-zCLINICAL EPIGENETICS11118