Abstract Insertions are rare chromosomal rearrangements resulting from a three breaks mechanism. The risk of chromosomal imbalance in the offspring is estimated to be 15–50%. We have identified a ...familial history of direct, paracentric intrachromosomal 9q insertion, balanced in healthy members. For intrachromosomal insertions, unbalanced products in the offspring are always recombinants and in our case, reciprocal deletion and duplication of the inserted segment (9q22.31–9q31.1) were observed. These imbalances involved several genes, including PTCH1. PTCH1 haploinsufficiency causes Gorlin syndrome, an autosomal dominant disorder usually linked to the gene mutation but sometimes due to a 9q deletion. Clinical findings are different in 9q deletions and duplications including PTCH1 , notably concerning the predisposition to benign and malignant tumors reported in the Gorlin syndrome. Furthermore, some features may be reciprocal. This history of intrachromosomal insertion highlights the importance of morphological cytogenetic analyses to provide an accurate genetic counseling.
Abstract Array-CGH has revealed a large number of copy number variations (CNVs) in patients with multiple congenital anomalies and/or mental retardation (MCA/MR). According to criteria recently ...listed, pathogenicity was clearly suspected for some CNVs but benign CNVs, considered as polymorphisms, have complicated the interpretation of the results. In this study, genomic DNAs from 132 French patients with unexplained mental retardation were analysed by genome wide high-resolution Agilent® 44K oligonucleotide arrays. The results were in accordance with those observed in previous studies: the detection rate of pathogenic CNVs was 14.4%. A non-random involvement of several chromosomal regions was observed. Some of the microimbalances recurrently involved regions (1q21.1, 2q23.1, 2q32q33, 7p13, 17p13.3, 17p11.2, 17q21.31) corresponding to known or novel syndromes. For all the pathogenic CNVs, further cases are needed to allow more accurate genotype–phenotype correlations underscoring the importance of databases to group patients with similar molecular data.
Abstract We report the case of a female patient exhibiting multiple congenital malformations including diaphragmatic hernia and heart defect. Cytogenetic studies (including karyotype, FISH and ...array-CGH) showed a de novo terminal deletion (6.9 Mb) on chromosome 15 in association with a recombinant X chromosome bearing a 9-Mb Xp duplication and a 46-Mb Xq deletion distal to XIST . The recombinant X chromosome was caused by a maternal inv(X)(p22.31q22.3). The X chromosome inactivation pattern was skewed in the patient suggesting a possible inactivation of the recombinant X chromosome. Considering these results, the phenotype was linked to the de novo terminal 15q deletion. These results strengthen the assumption that array-CGH should be applied to each fetus/newborn with multiple congenital malformations.
Abstract Terminal deletions of the long arm of chromosome 4 are associated with a recognizable phenotype consisting of dysmorphic facial features, cleft palate, upper and lower limb malformations, ...cardiac defects and growth and mental retardation. Here we report on two female patients, a mother and her daughter, carrying the same 4q34 → qter deletion but presenting with a different phenotype. The mother's presentation is consistent with previous findings in patients with terminal deletions of the long arm of chromosome 4. However, she presented at the age of 54 years with bilateral serous carcinoma of the Fallopian tubes, a rare gynaecologic cancer that might be attributed to the haploinsufficiency of the tumor suppressor gene FAT . The daughter presented isolated congenital aplasia of the uterus and vagina, the prime feature of the MRKH syndrome. This has not been described before in association with a 46,XX,del(4)(q34qter).
Infections increase morbidity and mortality in patients with autoimmune disorders; however, this association has not been established in rheumatic diseases and SARS-CoV-2 infection.
To describe the ...clinical characteristics and mortality of patients with rheumatic diseases and severe COVID-19.
Observational and descriptive case series in patients with rheumatic diseases and severe SARS-CoV-2 infection, confirmed by PCR or pulmonary tomography, hospitalized in Mexico City from March to August 2020.
15 patients with a mean age of 57 years (SD ± 11) were included, 66.6% were women, and 80% had a positive PCR test. The time from onset of symptoms to hospitalization, on average, was 7.2 days (SD ± 2.1). 46.6% died. Patients who died had a lower mean platelet level compared to survivors. The inflammatory reactants were higher in the deceased. There were no statistically significant differences in mortality for the variables related to rheumatic disease.
The differences in mortality of patients with severe COVID-19 in this series of cases seem to be related to the infection and not to the rheumatic disease.
In a previous study, we identified regions on the surface of tumor cells which act as acceptor sites for putrescine (Put) and studied the competition between structural analogs of Put ...(N,N'-tetramethyl-alpha,omega-diaminoalkanes) and Put bound to latex microspheres. A chain of four to seven carbons was necessary for inhibition of Put-latex binding to the cell surface of human glioblastoma (U251) cells. We show here that under the experimental conditions, N,N'-tetramethyl-1,4-butanediamine and N,N'-tetramethyl-1,7-heptanediamine exhibit an antitumor effect. In a first step (1-48 h after treatment), cells exposed to these compounds show large intracellular vacuoles. We failed to detect any acid phosphatase activity in these intracellular structures revealing that they were not lysosomes. Electron microscopy observations argue for the conclusion that these vacuoles are an hypertrophy of the endoplasmic reticulum (ER) and/or of the Golgi vesicles. Our hypothesis is that this typical effect of the analogs reveals that ER could be a physiological target of endogenous polyamines. At a later stage (6 days after treatment), the cells undergo morphological and biochemical changes: thin and long expansions characterize the cells and the GFA protein is overexpressed. Correlated to both these effects, karyotypic modifications are found in chromosomes 3 and 6. These changes evoke a differentiation of the treated cells. The work provides evidence that N-methylated polyamine analogs taking the place of endogenous putrescine demonstrate a hopeful antitumor effect.
We herein report a male patient known as having a XYY karyotype. At the age of 26 years a Prader–Willi syndrome (PWS) was diagnosed. Before that time the whole symptomatology was ascribed to the XYY ...syndrome. This is the first reported association of PWS and polygonosomal abnormality in a male adult (whose height is above average).
