Antiphospholipid Antibodies Are Major Risk Factors for Non-Thrombotic Cardiac Complications in Systemic Lupus Erythematosus.

In systemic lupus erythematosus (SLE), cardiovascular complications are among the leading causes of death. Cardiovascular risk in SLE is even higher in the presence of antiphospholipid antibodies or secondary antiphospholipid syndrome (APS). The aim of this retrospective, single-center study was to investigate the occurrence of antiphospholipid antibodies and non-thrombotic cardiac manifestations in 369 SLE patients. We also assessed the clinical and laboratory characteristics of the patients to reveal the risk factors for cardiac manifestations. Patients were divided into two groups based on the presence of antiphospholipid antibodies (APA); 258 (69.9%) patients were APA positive, and 111 (30.1%) patients were APA negative. Mitral and tricuspid insufficiency, aortic stenosis and pulmonary arterial hypertension were more common in APA-positive patients. Anticardiolipin IgG showed the strongest correlation with any non-thrombotic cardiac manifestations. Based on our results, the adjusted global antiphospholipid syndrome score (aGAPSS) above 8.5 is predictive of valvulopathies and ischemic heart disease, while aGAPSS above 9.5 is predictive of cardiomyopathies. The presence of antiphospholipid antibodies may affect the development of cardiac manifestations in SLE. Periodic cardiological and echocardiographic screening of patients without cardiac complaints, as well as regular monitoring of antiphospholipid antibodies, have great importance during the treatment of SLE patients.

Potent New Targets for Autophagy Enhancement to Delay Neuronal Ageing.

Autophagy is a lysosomal-dependent degradation process of eukaryotic cells responsible for breaking down unnecessary and damaged intracellular components. Autophagic activity gradually declines with age due to genetic control, and this change contributes to the accumulation of cellular damage at advanced ages, thereby causing cells to lose their functionality and viability. This could be particularly problematic in post-mitotic cells including neurons, the mass destruction of which leads to various neurodegenerative diseases. Here, we aim to uncover new regulatory points where autophagy could be specifically activated and test these potential drug targets in neurodegenerative disease models of Drosophila melanogaster. One possible way to activate autophagy is by enhancing autophagosome-lysosome fusion that creates the autolysosome in which the enzymatic degradation happens. The HOPS (homotypic fusion and protein sorting) and SNARE (Snap receptor) protein complexes regulate the fusion process. The HOPS complex forms a bridge between the lysosome and autophagosome with the assistance of small GTPase proteins. Thus, small GTPases are essential for autolysosome maturation, and among these proteins, Rab2 (Ras-associated binding 2), Rab7, and Arl8 (Arf-like 8) are required to degrade the autophagic cargo. For our experiments, we used Drosophila melanogaster as a model organism. Nerve-specific small GTPases were silenced and overexpressed. We examined the effects of these genetic interventions on lifespan, climbing ability, and autophagy. Finally, we also studied the activation of small GTPases in a Parkinson's disease model. Our results revealed that GTP-locked, constitutively active Rab2 (Rab2-CA) and Arl8 (Arl8-CA) expression reduces the levels of the autophagic substrate p62/Ref(2)P in neurons, extends lifespan, and improves the climbing ability of animals during ageing. However, Rab7-CA expression dramatically shortens lifespan and inhibits autophagy. Rab2-CA expression also increases lifespan in a Parkinson's disease model fly strain overexpressing human mutant (A53T) α-synuclein protein. Data provided by this study suggests that Rab2 and Arl8 serve as potential targets for autophagy enhancement in the Drosophila nervous system. In the future, it might be interesting to assess the effect of Rab2 and Arl8 coactivation on autophagy, and it would also be worthwhile to validate these findings in a mammalian model and human cell lines. Molecules that specifically inhibit Rab2 or Arl8 serve as potent drug candidates to modulate the activity of the autophagic process in treating neurodegenerative pathologies. In the future, it would be reasonable to investigate which GAP enzyme can inhibit Rab2 or Arl8 specifically, but not affect Rab7, with similar medical purposes.

[The institutional presence of music therapists in aphasia therapy in Hungary]. / Zeneterapeuták intézményi jelenléte a magyarországi aphasiaterápiában.

INTRODUCTION: Numerous international studies have reported on the relevance of music therapy for aphasia, but music-based therapy for the rehabilitation of acquired language and speech disorders is not common in the clinical practice of Hungary. OBJECTIVE: The aim of our study is to provide insights into the composition of professional teams involved in aphasia care in active neurology and stroke wards and rehabilitation departments in Hungarian hospitals, with a special focus on the presence of music therapists. We are looking for the answer to why the employment of music therapists in hospitals is so low in our country. METHOD: For our research, we selected the relevant institutions and departments from a list of hospitals on the website of the National Directorate General for Hospitals. Data were then collected from the websites of the hospital departments, supplemented or clarified with information from the head of department's physicians where necessary. RESULTS: None of the active neurology and stroke wards employ a music therapist. Two of the rehabilitation wards have a total of 4 music therapists. DISCUSSION: The low number of trained professionals in music therapy for aphasia is due to financial reasons, lack of professionals and lack of professional demand. CONCLUSION: Our research shows that music therapy is deeply underrepresented in the field of aphasia rehabilitation in Hungarian hospitals. The reasons for this are quite diverse and their elimination would require effective intervention in many areas. Orv Hetil. 2023; 164(19): 747-752.

Changes in Clinical Manifestations and Course of Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome over Three Decades.

Systemic lupus erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which potentially results in a more severe disease course and reduced life expectancy. Since the therapeutic guidelines have been refined in the last 15 years, we assumed that the diseases course has become more favorable. In order to shed light on these achievements, we compared the data of SLE patients diagnosed before and since 2004. In our retrospective study, we assessed a wide spectrum of clinical and laboratory data of 554 SLE patients who received regular follow-up care and therapy at our autoimmune center. Among these patients, 247 had antiphospholipid antibodies (APAs) without clinical signs of APS, and 113 had definitive APS. In the APS group, among patients diagnosed since 2004, deep vein thrombosis (p = 0.049) and lupus anticoagulant positivity (p = 0.045) were more frequent, while acute myocardial infarction was less frequent (p = 0.021) compared with patients diagnosed before 2004. Among the APA positive patients without definitive APS, anti-cardiolipin antibody positivity (p = 0.024) and development of chronic renal failure (p = 0.005) decreased in patients diagnosed since 2004. Our study demonstrates that the disease course has changed in recent years; however, in the presence of APS, we have to expect repeated thrombotic events despite adequate anticoagulant therapy.

In situ gelation of thiolated poly(aspartic acid) derivatives through oxidant-free disulfide formation for ophthalmic drug delivery.

Efficient topical treatment of ocular diseases requires a prolonged residence time of drug formulations. An in situ gelling, mucoadhesive system can provide improved residence time while keeps the installation of the formulation easy and accurate due to its low initial viscosity. We synthesized a two-component, biocompatible water-based liquid formulation showing in situ gelation upon mixing. S-protected, preactivated derivatives of thiolated poly(aspartic acid) (PASP-SS-MNA) were synthesized by coupling the free thiol groups of thiolated poly(aspartic acid) (PASP-SH) with 6-mercaptonicotinic acid (MNA). The amount of protecting groups was 242, 341, and 530 µmol/g depending on the degree of thiolation of PASP. The chemical interaction between PASP-SS-MNA and mucin was proven, indicating the mucoadhesive properties. Disulfide cross-linked hydrogels were formed in situ without an oxidizing agent by mixing the aqueous solutions of PASP-SS-MNA and PASP-SH. The gelation time was controlled between 1 and 6 min, while the storage modulus was as high as 4-16 kPa depending on the composition. Swelling experiments showed that hydrogels with no residual thiol groups are stable in phosphate-buffered saline at pH = 7.4. In contrast, the presence of free thiol groups leads to the dissolution of the hydrogel with a rate depending on the excess of thiol groups. The biological safety of the polymers and MNA was confirmed on Madin-Darby Canine Kidney cell line. Furthermore, a prolonged release of ofloxacin was observed at pH = 7.4 compared to a conventional liquid formulation, supporting the potential of the developed biopolymers in ophthalmic drug delivery.

Synthesis, complex formation and corneal permeation of cyclodextrin-modified, thiolated poly(aspartic acid) as self-gelling formulation of dexamethasone.

The present study aimed at developing a potential in situ gellable dexamethasone (DXM) eye drop. Poly(aspartic acid) (PASP) derivatives were synthesized with dual functionality to improve the solubility of DXM, and to achieve in situ gelation. First, amine-modified ß-cyclodextrin (CD) was attached to polysuccinimide (PSI), second, thiol functionalities were added by the reaction of cysteamine and succinimide rings. Finally, the PSI derivatives were hydrolysed to the corresponding PASP derivatives to get water-soluble polymers. Phase-solubility studies confirmed the complexation ability of CD-containing PASP derivatives. In situ gelation and the effect of the CD immobilization on this behaviour were characterized by rheological measurements. The solubilizing effect of CD was confirmed by kinetic solubility measurements, whereas in vitro corneal permeability assay (corneal-PAMPA) measurements were performed to determine in vitro permeability and flux values. The effect of the PASP derivatives on permeation strongly depended on chemical composition and polymer concentration.

Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility.

Pomalidomide (POM), a potent anticancer thalidomide analogue was characterized in terms of cyclodextrin complexation to improve its aqueous solubility and maintain its anti-angiogenic activity. The most promising cyclodextrin derivatives were selected by phase-solubility studies. From the investigated nine cyclodextrins - differing in cavity size, nature of substituents, degree of substitution and charge - the highest solubility increase was observed with sulfobutylether-ß-cyclodextrin (SBE-ß-CD). The inclusion complexation between POM and SBE-ß-CD was further characterized with a wide variety of state-of-the-art analytical techniques, such as nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), circular dichroism spectroscopy, fluorescence spectroscopy as well as X-ray powder diffraction method (XRD). Job plot titration by NMR and the AL-type phase-solubility diagram indicated 1:1 stoichiometry in a liquid state. Complementary analytical methods were employed for the determination of the stability constant of the complex; the advantages and disadvantages of the different approaches are also discussed. Inclusion complex formation was also assessed by molecular modelling study. Solid state complexation in a 1:1 M ratio was carried out by lyophilization and investigated by IR and XRD. The complex exhibited fast-dissolution with immediate release of POM, when compared to the pure drug at acidic and neutral pH. Kinetic analysis of POM release from lyophilized complex shows that Korsmeyer-Peppas and Weibull model described the best the dissolution kinetics. The cytotoxicity of the complex was tested against the LP-1 human myeloma cell line which revealed that supramolecular interactions did not significantly affect the anti-cancer activity of the drug. Overall, our results suggest that the inclusion complexation of POM with SBE-ß-CD could be a promising approach for developing more effective POM formulations with increased solubility.

Synthesis of 3-O-Carboxyalkyl Morphine Derivatives and Characterization of Their Acid-Base Properties.

The C-3 phenolic hydroxy group containing morphine derivatives (morphine, oxymorphone, naloxone, naltrexone) are excellent candidates for the synthesis of 3-O-functionalized molecules. Achieving free carboxylic group containing derivatives gives the opportunity for further modification and conjugation that could be used for immunization and immunoassays. For this purpose ethyl bromo- and chloroacetate can be used as O-alkylating agents. Hydrolyzing the products affords the appropriate free carboxylic group containing 3-O-carboxyalkyl derivatives. As these molecules contain an acidic and a basic functional group the protonation macro- and microconstants were determined too, using pH-potentiometry and NMR-pH titration, beside fully characterizing their structure using IR, CD, NMR and HR-MS measurements.

Generation of multiple iPSC clones from a male schizophrenia patient carrying de novo mutations in genes KHSRP, LRRC7, and KIR2DL1, and his parents.

Here we describe the generation of induced pluripotent stem cell lines from each member - male proband, mother, father - of a schizophrenia case-parent trio that participated in an exome sequencing study, and 3 de novo mutations were identified in the proband. Peripheral blood mononuclear cells were obtained from all three individuals and reprogrammed using Sendai virus particles carrying the Yamanaka transgenes. These 3 iPSC lines (iPSC-SZ-HU-MO 1, iPSC-SZ-HU-FA 1, and iPSC-SZ-HU-PROB 1) represent a resource for examining the functional significance of the identified de novo mutations in the molecular pathophysiology of schizophrenia.

Clinical and genetic findings in Hungarian pediatric patients carrying chromosome 16p copy number variants and a review of the literature.

The short arm of chromosome 16 (16p) is enriched for segmental duplications, making it susceptible to recurrent, reciprocal rearrangements implicated in the etiology of several phenotypes, including intellectual disability, speech disorders, developmental coordination disorder, autism spectrum disorders, attention deficit hyperactivity disorders, obesity and congenital skeletal disorders. In our clinical study 73 patients were analyzed by chromosomal microarray, and results were confirmed by fluorescence in situ hybridization or polymerase chain reaction. All patients underwent detailed clinical evaluation, with special emphasis on behavioral symptoms. 16p rearrangements were identified in 10 individuals. We found six pathogenic deletions and duplications of the recurrent regions within 16p11.2: one patient had a deletion of the distal 16p11.2 region associated with obesity, while four individuals had duplications, and one patient a deletion of the proximal 16p11.2 region. The other four patients carried 16p variations as second-site genomic alterations, acting as possible modifying genetic factors. We present the phenotypic and genotypic results of our patients and discuss our findings in relation to the available literature.

Development and Characterization of Potential Ocular Mucoadhesive Nano Lipid Carriers Using Full Factorial Design.

Generally, topically applied eye drops have low bioavailability due to short residence time and low penetration of the drug. The aim of the present study was to incorporate dexamethasone (DXM) into nano lipid carriers (NLC), which contain mucoadhesive polymer, in order to increase the bioavailability of the drug. A 23 factorial experimental design was applied, in which the three factors were the polymer, the DXM, and the emulsifier concentrations. The samples were analyzed for particle size, zeta potential, polydispersity index, and Span value. The significant factors were identified. The biocompatibility of the formulations was evaluated with human corneal toxicity tests and immunoassay analysis. The possible increase in bioavailability was analyzed by means of mucoadhesivity, in vitro drug diffusion, and different penetration tests, such as in vitro cornea PAMPA model, human corneal cell penetration, and ex vivo porcine corneal penetration using Raman mapping. The results indicated that DXM can be incorporated in stable mucoadhesive NLC systems, which are non-toxic and do not have any harmful effect on cell junctions. Mucoadhesive NLCs can create a depot on the surface of the cornea, which can predict improved bioavailability.

The Chlorination of N-Methyl Amino Acids with Hypochlorous Acid: Kinetics and Mechanisms.

The formation and decomposition kinetics of N-chloro-N-methyl amino acids were studied to predict the fate and impact of these compounds in water treatment technologies and biological systems. These compounds form in fast second-order reactions between N-methyl amino acids and hypochlorous acid. The comparison of the activation parameters for the reactions of N-methyl substituted and nonsubstituted branched-chain amino acids reveals the transition-state features less organized structure and stronger bonds between the reactants in the reactions with the N-methyl derivatives. This is due to a combined positive inductive effect of the N-methyl group and the alkyl side chain as well as to the steric effects of the substituents. N-Methyl-N-chloro amino acids decompose much faster than the nonsubstituted compounds. The reaction rates do not depend on the pH, and the same final product is formed in the entire pH range. N-Chlorosarcosine is an exception, as it decomposes via competing paths, kdobs = kd + kdOH[OH-], yielding different final products. This feature is most likely due to the lack of an alkyl substituent on the α-carbon atom. Under physiological pH, aldehydes and methylamine form in these reactions, which are not particularly toxic.

Reversed-phase HPLC enantioseparation of pantoprazole using a teicoplanin aglycone stationary phase-Determination of the enantiomer elution order using HPLC-CD analyses.

A direct HPLC method was developed for the enantioseparation of pantoprazole using macrocyclic glycopeptide-based chiral stationary phases, along with various methods to determine the elution order without isolation of the individual enantiomers. In the preliminary screening, four macrocyclic glycopeptide-based chiral stationary phases containing vancomycin (Chirobiotic V), ristocetin A (Chirobiotic R), teicoplanin (Chirobiotic T), and teicoplanin-aglycone (Chirobiotic TAG) were screened in polar organic and reversed-phase mode. Best results were achieved by using Chirobiotic TAG column and a methanol-water mixture as mobile phase. Further method optimization was performed using a face-centered central composite design to achieve the highest chiral resolution. Optimized parameters, offering baseline separation (resolution = 1.91 ± 0.03) were as follows: Chirobiotic TAG stationary phase, thermostated at 10°C, mobile phase consisting of methanol/20mM ammonium acetate 60:40 v/v, and 0.6 mL/min flow rate. Enantiomer elution order was determined using HPLC hyphenated with circular dichroism (CD) spectroscopy detection. The online CD signals of the separated pantoprazole enantiomers at selected wavelengths were compared with the structurally analogous esomeprazole enantiomer. For further verification, the inline rapid, multiscan CD signals were compared with the quantum chemically calculated CD spectra. Furthermore, docking calculations were used to investigate the enantiorecognition at molecular level. The molecular docking shows that the R-enantiomer binds stronger to the chiral selector than its antipode, which is in accordance with the determined elution order on the column-S- followed by the R-isomer. Thus, combined methods, HPLC-CD and theoretical calculations, are highly efficient in predicting the elution order of enantiomers.

Design and Optimization of Nanostructured Lipid Carrier Containing Dexamethasone for Ophthalmic Use.

The aim of this study was to perform a preformulation study of dexamethasone (DXM)-loaded nanostructured lipid carriers (NLCs) for ocular use. Lipid screening was applied to find the most suitable solid and liquid lipids and surfactant for the NLC formulation. The visual observation was proved with XRD measurements for the establishment of the soluble state of DXM. Thermoanalytical measurements indicated that the most relevant depression of the crystallinity index could be ensured when using a 7:3 solid lipid:oil ratio. In order to optimize the NLC composition, a 23 full factorial experimental design was used. It was established that each independent factor (lipid, DXM, and surfactant concentration) had a significant effect on the particle size while in the case of entrapment efficiency, the DXM and surfactant concentrations were significant. Lower surfactant and lipid concentrations could be beneficial because the stability and the entrapment efficacy of NLCs were more favorable. The toxicity tests on human cornea cells indicated good ophthalmic tolerability of NLCs. The in vitro drug release study predicted a higher concentration of the solute DXM on the eye surface while the Raman mapping penetration study on the porcine cornea showed a high concentration of nanocarriers in the hydrophylic stroma layer.

Analysis of aristolochlic acids and evaluation of antibacterial activity of Aristolochia clematitis L.

INTRODUCTION: Several Aristolochia species were used as medicinal herb across Europe and in recent years, their antimicrobial activity has also been investigated. MATERIALS AND METHODS: In this study, A. clematitis was selected to evaluate the aristolochic acids I and II (AA I and AA II) concentrations and the antimicrobial activity of methanol, hexane, butanol, and ethyl acetate extracts of the root, stem, leaf, root, and fruit. AA I and AA II contents were measured by a validated high-performance liquid chromatography-ultraviolet method. RESULTS: Each fraction of the plant contained AA I and AA II and the root was found to have the highest contents of AA I (1.09%) and AA II (0.7454%). The minimum inhibitory concentrations of all extracts were determined by standard microdilution method. The fruit's extracts showed the most efficient antimicrobial effect against both methicillin sensitive and resistant Staphylococcus aureus strains. CONCLUSION: Correlation between the AA I and AA II concentrations and the antimicrobial effect was not found.

Mucoadhesive Cyclodextrin-Modified Thiolated Poly(aspartic acid) as a Potential Ophthalmic Drug Delivery System.

Thiolated poly(aspartic acid) is known as a good mucoadhesive polymer in aqueous ophthalmic formulations. In this paper, cyclodextrin-modified thiolated poly(aspartic acid) was synthesized for the incorporation of prednisolone, a lipophilic ophthalmic drug, in an aqueous in situ gellable mucoadhesive solution. This polymer combines the advantages of cyclodextrins and thiolated polymers. The formation of the cyclodextrin-drug complex in the gels was analyzed by X-ray powder diffraction. The ocular applicability of the polymer was characterized by means of physicochemical, rheological and drug diffusion tests. It was established that the chemical bonding of the cyclodextrin molecule did not affect the complexation of prednisolone, while the polymer solution preserved its in situ gellable and good mucoadhesive characteristics. The chemical immobilization of cyclodextrin modified the diffusion profile of prednisolone and prolonged drug release was observed. The combination of free and immobilized cyclodextrins provided the best release profile because the free complex can diffuse rapidly, while the bonded complex ensures a prolonged action.

DNA binding of sunitinib: Spectroscopic evidence via circular dichroism and nuclear magnetic resonance.

Sunitinib is a non-selective tyrosine kinase inhibitor, but in its chemical structure there can be discovered certain features, which suggest the ability to bind to DNA. These elements are the planar aromatic system and the tertiary amine function, which is protonated at the pH of the organism. In this study, the binding of the drug sunitinib to DNA was investigated using circular dichroism (CD), 1H NMR and UV spectroscopies, along with CD melting. For these studies DNA was isolated from calf thymus (CT), salmon fish sperm (SS), and chicken erythrocyte (CE), however for our purposes an artificially constructed and highly purified plasmid DNA (pUC18) preparation proved to be the most suitable. DNA binding of the drug was confirmed by shifts in the characteristic CD bands of the DNA, the appearance of an induced CD (ICD) signal in the upper absorption region of sunitinib (300 nm-500 nm), and the evidence from CD melting studies and the NMR. Based on the CD and NMR measurements, it can be assumed that sunitinib has a multiple-step binding mechanism.

Complex X chromosome rearrangement associated with multiorgan autoimmunity.

BACKGROUND: Turner syndrome, a congenital condition that affects 1/2,500 births, results from absence or structural alteration of the second sex chromosome. Turner syndrome is usually associated with short stature, gonadal dysgenesis and variable dysmorphic features. The classical 45,X karyotype accounts approximately for half of all patients, the remainder exhibit mosaicism or structural abnormalities of the X chromosome. However, complex intra-X chromosomal rearrangements involving more than three breakpoints are extremely rare. RESULTS: We present a unique case of a novel complex X chromosome rearrangement in a young female patient presenting successively a wide range of autoimmune diseases including insulin dependent diabetes mellitus, Hashimoto's thyroiditis, celiac disease, anaemia perniciosa, possible inner ear disease and severe hair loss. For the genetic evaluation, conventional cytogenetic analysis and FISH with different X specific probes were initially performed. The complexity of these results and the variety of autoimmune problems of the patient prompted us to identify the exact composition and breakpoints of the rearranged X as well as methylation status of the X chromosomes. The high resolution array-CGH (assembly GRCh37/hg19) detected single copy for the whole chromosome X short arm. Two different sized segments of Xq arm were present in three copies: one large size of 80,3 Mb from Xq11.1 to Xq27.3 region and another smaller (11,1 Mb) from Xq27.3 to Xq28 region. An 1,6 Mb Xq27.3 region of the long arm was present in two copies. Southern blot analysis identified a skewed X inactivation with ≈ 70:30 % ratios of methylated/unmethylated fragments. The G-band and FISH patterns of the rearranged X suggested the aspect of a restructured i(Xq) chromosome which was shattered and fortuitously repaired. The X-STR genotype analysis of the family detected that the patient inherited intact maternal X chromosome and a rearranged paternal X chromosome. The multiple Xq breakages and fusions as well as inverted duplication would have been expected to cause a severe Turner phenotype. However, the patient lacks many of the classic somatic features of Turner syndrome, instead she presented multiorgan autoimmune diseases. CONCLUSIONS: The clinical data of the presented patient suggest that fragmentation of the i(Xq) chromosome elevates the risk of autoimmune diseases.

A de novo atypical ring sSMC(22) characterized by array CGH in a boy with cat-eye syndrome.

BACKGROUND: Microduplications 22q11 have been characterized as a genomic duplication syndrome mediated by nonallelic homologous recombination between region-specific low-copy repeats. Here we report on a 19 years old boy with intellectual disability having an unexpected structurally complex ring small supernumerary marker chromosome (sSMC) originated from a larger trisomy and a smaller tetrasomy of proximal 22q11 harboring additional copies of cat eye syndrome critical regions genes. RESULTS: PRINCIPAL CLINICAL FEATURES WERE: anorectal and urogenital malformations, total anomalous pulmonary venous return with secundum ASD, hearing defect, preauricular pits, seizure and eczema. The proband also presented some rare or so far not reported clinical findings such as hyperinsulinaemia, severe immunodeficiency and grave cognitive deficits. Chromosome analysis revealed a mosaic karyotype with the presence of a small ring-like marker in 60% of cells. Array CGH detected approximately an 1,2 Mb single and a 0,2 Mb double copy gain of the proximal long arm of chromosome 22. The 1,3 Mb intervening region of chromosome 22 from centromere to the breakpoints showed no copy alteration. The karyotype of the patient was defined as 47,XY,+mar[60]/46,XY[40].ish idic r(22)(q11.1.q11.21) × 4.arr 22q11(17,435, 645-18,656,678) × 3,(17,598,642-17,799,783) × 4 dn. CONCLUSIONS: The present report is the first one with a detailed description of clinical presentation in a patient carrying an atypical size ring sSMC (22) analyzed by array CGH. The specialty of the finding is emphasized by the fact that although the patient had a mosaic sSMC and the amplified region was smaller than in typical cat eye syndrome cases, the clinical presentation was severe.