MYH7‐related disease (MRD) is the most common hereditary primary cardiomyopathy (CM), with pathogenic MYH7 variants accounting for approximately 40% of familial hypertrophic CMs. MRDs may also ...present as skeletal myopathies, with or without CM. Since pathogenic MYH7 variants result in highly variable clinical phenotypes, from mild to fatal forms of cardiac and skeletal myopathies, genotype–phenotype correlations are not always apparent, and translation of the genetic findings to clinical practice can be complicated. Data on genotype–phenotype correlations can help facilitate more specific and personalized decisions on treatment strategies, surveillance, and genetic counseling. We present a series of six MRD pedigrees with rare genotypes, encompassing various clinical presentations and inheritance patterns. This study provides new insights into the spectrum of MRD that is directly translatable to clinical practice.
The term isolated ectopia lentis (EL; subluxation or dislocation of the human crystalline lens) is applied to patients with EL, without skeletal features and in the absence of aortic root dilatation. ...To date, the only gene shown to cause autosomal-recessive isolated EL is ADAMTSL4. Here we report a novel founder mutation in ADAMTSL4 gene in children of Bukharian Jewish origin presenting with early-onset bilateral EL. A carrier frequency of 1:48 was determined among unrelated healthy Bukharian Jews. Given the complications associated with disease and the allele frequency, a population screening for individuals of this ancestry is warranted in order to allow prenatal, pre-implantation or early postnatal diagnosis.
•A novel founder mutation in ADAMTSL4 is reported in children of Jewish Bukharian origin.•ADAMTSL4 founder mutation causes early-onset bilateral ectopia lentis.•A carrier frequency of 1:48 was determined among unrelated healthy Bukharian Jews.•Population screening for individuals of Bukharian Jewish ancestry is warranted.
ABSTRACT
Warburg Micro syndrome and Martsolf syndrome (MS) are heterogeneous autosomal‐recessive developmental disorders characterized by brain, eye, and endocrine abnormalities. Causative biallelic ...germline mutations have been identified in RAB3GAP1, RAB3GAP2, or RAB18, each of which encode proteins involved in membrane trafficking. This report provides an up to date overview of all known disease variants identified in 29 previously published families and 52 new families. One‐hundred and forty‐four Micro and nine Martsolf families were investigated, identifying mutations in RAB3GAP1 in 41% of cases, mutations in RAB3GAP2 in 7% of cases, and mutations in RAB18 in 5% of cases. These are listed in Leiden Open source Variation Databases, which was created by us for all three genes. Genotype–phenotype correlations for these genes have now established that the clinical phenotypes in Micro syndrome and MS represent a phenotypic continuum related to the nature and severity of the mutations present in the disease genes, with more deleterious mutations causing Micro syndrome and milder mutations causing MS. RAB18 has not yet been linked to the RAB3 pathways, but mutations in all three genes cause an indistinguishable phenotype, making it likely that there is some overlap. There is considerable genetic heterogeneity for these disorders and further gene identification will help delineate these pathways.
Warburg Micro syndrome (OMIM 60018) and Martsolf syndrome (OMIM 21270) are related autosomal recessive neurodevelopmental disorders. Micro syndrome is more severe and characterized by ocular (microphthalmos, microcornea, congenital cataracts and optic atrophy) and neurodevelopmental pathology (microcephaly, polymicrogyria, hypogenesis of the corpus callosum, severe learning disability and progressive limb spasticity) and hypothalamic hypogonadism. Causative germline mutations have been identified in RAB3GAP1 (41% of families), RAB3GAP2 (7% of families) and RAB18 (5% of families) and result in a strikingly consistent phenotype.
AIM： TO assess the effect of iron reduction after phlebotomy in rats with ＂normal＂ hepatic iron concentration （HIC） on the progression of hepatic fibrosis, as a result of bile duct ligation （BDL）. ...METHODS： Rats underwent phlebotomy before or after sham operation or BDL. Animals undergone only BDL or sham operation served as controls. Two weeks after surgery, indices of hepatic damage and fibrosis were evaluated. RESULTS： Phlebotomy lowered HIC. Phlebotomy after BDL was associated with body weight increase, lower hepatic weight, less portal hypertension, less periportal necrosis, less portal inflammation, lower hepatic activity index score and higher albumin levels. On the other hand, phlebotomy before BDL was associated with body weight decrease and hepatic activity index score increase. Phlebotomy after sham operation was not associated with any hepatic or systemic adverse effects. CONCLUSION： Reduction of HIC after induction of liver damage may have beneficial effects in BDL rats. However, iron deficiency could induce impairment of liver function and may make the liver more susceptible to insults like BDL.
Warburg Micro syndrome and Martsolf syndrome (MS) are heterogeneous autosomal-recessive developmental disorders characterized by brain, eye, and endocrine abnormalities. Causative biallelic germline ...mutations have been identified in RAB 3 GAP 1, RAB 3 GAP 2, or RAB 18, each of which encode proteins involved in membrane trafficking. This report provides an up to date overview of all known disease variants identified in 29 previously published families and 52 new families. One-hundred and forty-four Micro and nine Martsolf families were investigated, identifying mutations in RAB 3 GAP 1 in 41% of cases, mutations in RAB 3 GAP 2 in 7% of cases, and mutations in RAB 18 in 5% of cases. These are listed in Leiden Open source Variation Databases, which was created by us for all three genes. Genotype-phenotype correlations for these genes have now established that the clinical phenotypes in Micro syndrome and MS represent a phenotypic continuum related to the nature and severity of the mutations present in the disease genes, with more deleterious mutations causing Micro syndrome and milder mutations causing MS. RAB18 has not yet been linked to the RAB3 pathways, but mutations in all three genes cause an indistinguishable phenotype, making it likely that there is some overlap. There is considerable genetic heterogeneity for these disorders and further gene identification will help delineate these pathways. Warburg Micro syndrome (OMIM 60018) and Martsolf syndrome (OMIM 21270) are related autosomal recessive neurodevelopmental disorders. Micro syndrome is more severe and characterized by ocular (microphthalmos, microcornea, congenital cataracts and optic atrophy) and neurodevelopmental pathology (microcephaly, polymicrogyria, hypogenesis of the corpus callosum, severe learning disability and progressive limb spasticity) and hypothalamic hypogonadism. Causative germline mutations have been identified in RAB3GAP1 (41% of families), RAB3GAP2 (7% of families) and RAB18 (5% of families) and result in a strikingly consistent phenotype.
The likelihood of recurrence in breast cancer patients with hormone receptor-positive (HR-positive) tumors is influenced by clinical, histopathological, and molecular features. Recent studies ...suggested that activated STAT3 (pSTAT3) might serve as a biomarker of outcome in breast cancer patients. In the present work, we have analyzed the added value of pSTAT3 to OncotypeDx Recurrence Score (RS) in patient prognostication. We have found that patients with low RS (<26) and low pSTAT3 might represent a population at a higher risk for cancer recurrence. Furthermore, we have observed that a positive pSTAT3 score alone can be a favorable marker for patients with HR-positive breast cancer under the age of 50. In an era of personalized medicine, these findings warrant further appraisal of chemotherapy benefit in this population.
Display omitted
•Hyperbranched polyglycidol is less associative than linear polyglycidol (PGL).•Hyperbranched and linear polyglycidol interact with SDS.•The strongest interaction with SDS occurs for ...the shortest linear polyglycidol.•The cavities in hyperbranched PGL may host probes of appropriate size.
Linear and hyperbranched polyglycidol (LPGL and HPGL) with average molecular weight of a few thousands were studied in water and surfactant solutions. The employed surfactants are hexaethyleneglycol mono n-dodecyl ether (C12E6), cetyl trimethyl ammonium bromide (CTAB) and sodium dodecyl sulfate (SDS). The working methods are surface tension, steady-state fluorescence, dynamic light scattering (DLS), electrokinetic potential and FTIR spectroscopy. The linear polyglycidols are weakly associative species, unlike the hyperbranched one which is more hydrophilic and harder associates. The linear polymers most efficiently interact with the anionic surfactant, followed by cationic and most weakly with the nonionic. The hydrodynamic diameters of the investigated polyglycidols depend on their structure and molecular weight. In the presence of SDS, the hydrodynamic diameters vary with surfactant concentration. The study reveals the solubilization of fluorescent probes (pyrene, naphthalene) inside the polyglycidol aggregates. Unlike the LPGL, the presence of cavities in HPGL macromolecule offers supplementary “pockets” for solubilization.
PDF
