Analysis of Sleep Quality, Mood Alterations and modifications of some Habits/Behavior during two different Periods of the COVID-19 Pandemic in Argentina / Análisis de la calidad del sueño, alteraciones del humor y modificaciones de algunos hábitos y conductas durante dos diferentes períodos de la pandemia por COVID-19 en Argentina.

The pandemic caused by COVID-19 in the world, in its different periods, produced many changes in sleep and in various areas of mental health. Objectives: To evaluate and to compare sleep quality and aspects of mental health during two different periods of the COVID-19 pandemic, as well as to analyze some changes in habits/behaviors. Subjects and methods: A cross-sectional study was carried out, through an anonymous survey. Demographic information, sleep quality, depressive and anxiety symptoms were analyzed. Of the total, 998 surveys were selected. The survey focused on 2 time periods, from March to July 2020 and from March to July 2021. Results: When sleep quality was compared during the 2020 versus 2021 periods, the percentage of poor sleepers went from 51% to 59% in the second period. Regarding depressive symptoms, it went from 21.1 to 16.3% and the percentage of anxiety symptoms went from 59.5 to 47.6%. Poor sleep quality affected more people in 2021 compared to 2020. The percentage of participants with symptoms of anxiety and depression decreased in 2021. People changed some habits/behaviors, such as: changing routine schedules, acquiring pets, sharing their dreams more, and remembering them more frequently. This article contributes to knowing various aspects of sleep, mood swings and changes in habits/behaviors that occurred during the pandemic in Argentina.

La pandemia provocada por COVID-19 en el mundo, en sus diferentes períodos, produjo muchos cambios en el sueño y en diversas áreas de la salud mental. Objetivos: Evaluar y comparar calidad de sueño y aspectos de la salud mental durante dos períodos diferentes de la pandemia por COVID-19, como así también analizar algunos cambios en hábitos/conductas. Materiales y métodos: Se realizó un estudio de corte transversal, a través de una encuesta anónima de la que participaron 998 personas. La misma se realizó en dos períodos de tiempo. El primer período comprendió de marzo a julio de 2020, el segundo período abarcó de marzo a julio 2021. El análisis consideró: información demográfica, calidad del sueño, síntomas depresivos y de ansiedad. Resultados: Al comparar la calidad de sueño durante los períodos 2020 versus el 2021, el porcentaje de malos dormidores pasó del el 51% al 59% en el segundo período. En cuanto a los síntomas depresivos pasó del 21,1 al 16,3% y el porcentaje de síntomas de ansiedad pasó del 59,5 al 47,6%. La mala calidad del sueño afectó a un número mayor de personas en el 2021 que en el 2020 mientras que el porcentaje de participantes con síntomas de ansiedad y de depresión disminuyó en el año 2021. En la segunda fase de la encuesta las personas modificaron algunos hábitos/conductas como ser: cambiaron horarios de rutina, adquirieron mascotas, compartieron más sus sueños y recordaban con mayor frecuencia los mismos. Este artículo contribuye a conocer diversos aspectos del sueño, los cambios de humor y modificaciones de hábitos/conductas que ocurrieron durante la pandemia en Argentina.

Survey of medical genetic services in Italy: year 2011.

BACKGROUND: The aim of this study was to collect information about 2011 genetic activities in Italy, with the purpose of providing guidance to the national health systems in order to improve genetic services. METHODS: A web-based survey was carried out to achieve the information. RESULTS: Data were collected from 268 macrostructures hosting 517 services and employing 3246 persons. About 295,000 cytogenetic, 35,000 immunogenetic and 263,000 molecular genetic analyses of 902 genes were recorded. Seventy-four percent of the services were accredited with institutional bodies and 57 % were also certified according to ISO 9001 standard. Twenty percent of cytogenetic laboratories had participated in an European External Quality Assessment (EQA) while 44 % participated in a national EQA. Only 28 % of the molecular laboratories had participated in a national Cystic Fibrosis EQA. The percentage of diagnoses confirmed by genetic tests varied among disorders, ranging from 52 % for coeliac disease to 4 % for fragile X syndrome. CONCLUSIONS: This study highlights the need for reorganizing the Italian genetic services network, improving EQA participation and developing national plans for implementing next generation technologies. Concerted effort has to be addressed in the education of the professionals prescribing tests to improve appropriateness and to inform patients, who now have exposure to direct-to-consumer multifactorial genetic testing where clinical utility is unproven.

A novel mosaic NSD1 intragenic deletion in a patient with an atypical phenotype.

Sotos syndrome, which is characterized by overgrowth, macrocephaly, distinctive facial features, and developmental delay, arises from mutations and deletions of the NSD1 gene at 5q35.3. Sixteen NSD1 intragenic deletions (including one in a mosaic condition) and one partial duplication have been reported in patients with Sotos syndrome. Here, we describe a boy aged 4 years and 10 months that showed facial dysmorphism (including frontal bossing, widely spaced eyes, deeply set eyes, a wide nasal bridge, anteverted nares, and a wide mouth), normal growth, and a psychomotor delay. High-resolution array comparative genomic hybridization (CGH) analysis identified a mosaic heterozygous intragenic NSD1 deletion of 38 kb, which included part of intron 2 and the entire exon 3, and led to NSD1 haploinsufficiency. The deletion somatic mosaicism was subsequently confirmed by fluorescence in situ hybridization (FISH) analysis using fosmid clones. This patient presents the most atypical phenotype thus far associated with NSD1 haploinsufficiency. It is possible that this atypical phenotype may have resulted from the somatic mosaicism of the NSD1 defect. Our study confirms the usefulness of array CGH for increasing the detection rate of NSD1 abnormalities and for diagnosing syndromic patients that do not present an easily recognized phenotype.

Biocompatible fluorescent nanoparticles for in vivo stem cell tracking.

Efficient application of stem cells to the treatment of neurodegenerative diseases requires safe cell tracking to follow stem cell fate over time in the host environment after transplantation. In this work, for the first time, fluorescent and biocompatible methyl methacrylate (MMA)-based nanoparticles (fluoNPs) were synthesized through a free-radical co-polymerization process with a fluorescent macromonomer obtained by linking Rhodamine B and hydroxyethyl methacrylate. We demonstrate that the fluoNPs produced by polymerization of MMA-Rhodamine complexes (1) were efficient for the labeling and tracking of multipotent human amniotic fluid cells (hAFCs); (2) did not alter the main biological features of hAFCs (such as viability, cell growth and metabolic activity); (3) enabled us to determine the longitudinal bio-distribution of hAFCs in different brain areas after graft in the brain ventricles of healthy mice by a direct fluorescence-based technique. The reliability of our approach was furthermore confirmed by magnetic resonance imaging analyses, carried out by incubating hAFCs with both superparamagnetic iron oxide nanoparticles and fluoNPs. Our data suggest that these finely tunable and biocompatible fluoNPs can be exploited for the longitudinal tracking of stem cells.

Exploring patterns of unwanted behaviours in adults with Prader-Willi syndrome.

BACKGROUND: Obsessive-compulsive (O-C) traits, and excessive food intake are well known behavioural manifestations among individuals with Prader-Willi Syndrome (PWS). Other unwanted behaviours are also frequently observed, but they need a more specific investigation, especially in the adult population. METHODS: The behaviour of 31 PWS adults was investigated via the Symptom Checklist-90-Revised (SCL-90-R), the Yale-Brown Obsessive Compulsive Scale Symptom Checklist (Y-BOCS-SC), and the Prader-Willi Behavioural Checklist (PBC). The PBC is a quick screening questionnaire prompted specifically for the investigation on adults with PWS. RESULTS: Statistical clustering revealed two patterns of unwanted behaviours from the PBC. Behaviours belonging to the first cluster (e.g., Excessive food intake, Skin picking) appear to be linked to the usual phenotypic manifestation of PWS. By contrast, many other behaviours (e.g., some O-C symptoms and aggressive actions) could show a relationship also to individual psychopathologies. CONCLUSIONS: Both internal (Anxiety and Depression) and external (Hostility) difficulties in managing impulses should account for individually distinct behaviours in adults with PWS.

Electroclinical pattern in MECP2 duplication syndrome: eight new reported cases and review of literature.

PURPOSE: Duplications encompassing the MECP2 gene on the Xq28 region have been described in male patients with moderate to severe mental retardation, absent speech, neonatal hypotonia, progressive spasticity and/or ataxia, recurrent severe respiratory infections, gastrointestinal problems, mild facial dysmorphisms (midface hypoplasia, depressed nasal bridge, large ears) and epilepsy. Epilepsy can occur in >50% of cases, but the types of seizures and the electroclinical findings in affected male individuals have been poorly investigated up to the present. Herein we describe eight patients with MECP2 duplication syndrome and a specific clinical and electroencephalographic pattern. METHODS: Array CGH of genomic DNA from the probands was performed, and an Xq28 duplication ranging from 209 kb to 6.36 Mb was found in each patient. Electroencephalography studies and clinical and seizure features of all the patients were analyzed. KEY FINDINGS: We found that epilepsy tended to occur between late childhood and adolescence. Episodes of loss of tone of the head and/or the trunk were the most represented seizure types. Generalized tonic-clonic seizures were rarely observed. The typical interictal EEG pattern showed abnormal background activity, with generalized slow spike and wave asynchronous discharge with frontotemporal predominance. Sleep electroencephalography studies also demonstrated abnormal background activity; spindles and K complex were often abnormal in morphology and amplitude. Response to therapy was generally poor and drug resistance was a significant feature. SIGNIFICANCE: Although these cases and a review of the literature indicate that epilepsy associated with MECP2 duplication syndrome cannot be considered a useful marker for early diagnosis, epilepsy is present in >90% of adolescent patients and shows a peculiar electroclinical pattern. Consequently, it should be considered a significant sign of the syndrome, and an EEG follow-up of these patients should be encouraged from early childhood. Moreover, the definition of a more specific epileptic phenotype could be useful in order to suspect MECP2 duplication syndrome in older undiagnosed patients.

The "respiratory REM sleep without atonia benefit" on coexisting REM sleep behavior disorder - obstructive sleep apnea.

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by dream-enactment behaviors that emerge during a loss of REM sleep atonia. In patients with RBD, obstructive sleep apneas syndrome (OSAS) frequently occurs as a comorbid entity. It has been reported that the presence of muscle tone during REM sleep (REM sleep without atonia-RSWA) could play a protective role in patients with OSAS RBD. In OSAS, recurrent episodes of complete or partial collapse of the upper airway occur during both, NREM and REM sleep. Particularly during sleep, the withdrawal of excitatory noradrenergic and serotoninergic inputs to the upper airway motor neurons deeply reduces the pharyngeal muscle activity, increasing the propensity for superior airway collapse. The present study compared for the first time the impact of OSAS in RBD patients with a subtype of OSAS patients with predominantly or isolated REM sleep-related OSAS (OSAS REM group) in the search of an adequate model to evaluate future therapeutic strategies. Our study found a significant lower nadir of oximetry values in OSAS RBD in comparison with the OSAS REM group. This reduction, that we called the "respiratory RSWA benefit", is in accordance with the decrease of the nadir oximetry values observed in patients with Parkinson disease and OSAS with or without RBD. We suggest that the group of OSAS REM patients is a natural model to evaluate the respiratory protective role of RSWA in patients with coexisting RBD-OSAS and Parkinson's disease.

Genetic investigations on 8 patients affected by ring 20 chromosome syndrome.

BACKGROUND: Mosaic Chromosome 20 ring [r(20)] is a chromosomal disorder associated with a rare syndrome characterized by a typical seizure phenotype, a particular electroclinical pattern, cognitive impairment, behavioural problems and absence of a consistent pattern of dysmorphology. The pathogenic mechanism underlying seizures disorders in r(20) syndrome is still unknown. We performed a detailed clinical and genetic study on 8 patients with r(20) chromosome, aimed at detecting the genetic mechanism underlying r(20) syndrome. METHODS: We submitted 8 subjects with a previous diagnosis of ring 20 chromosome mosaicism to a clinical re-evaluation, followed by cytogenetic, FISH, array-CGH and molecular analyses. The genetic study was also extended to their available parents. RESULTS: FISH and array-CGH experiments indicate that cryptic deletions on chromosome 20 are not the cause of the r(20) chromosome associated disease. Moreover, no evidence of chromosome 20 uniparental disomy was found. Analysis of FISH signals given by variant in size alphoid tandem repeats probes on the normal chromosome 20 and the r(20) chromosome in the mosaic carriers suggests that the r(20) chromosome is the same chromosome not circularized in the "normal" cell line. CONCLUSIONS: Higher percentages of r(20) chromosome cells were observed to be related with precocious age at seizure onset and with resistance to antiepileptic drug treatment. Behavioural problems also seem to be associated with higher percentages of r(20) chromosome cells. Our results suggest that an epigenetic mechanism perturbing the expression of genes close to the telomeric regions, rather than deletion of genes located at the distal 20p and/or 20q regions, may underlie the manifestation of r(20) syndrome.

The endless quarantine: the impact of the COVID-19 outbreak on healthcare workers after three months of mandatory social isolation in Argentina.

OBJECTIVES: At the end of 2019 the SARS-CoV-2 outbreak spread around the globe with a late arrival to South America. The objective of this study was to evaluate the impact of the long period of mandatory social isolation that took place in Argentina on the general psychological well-being of healthcare workers due to the COVID-19 pandemic. METHODS: A survey was conducted during June 2020, in healthcare workers. Pittsburgh Sleep Quality Index, Insomnia Severity Index, Sleepiness-Wakefulness Inability and Fatigue Test, and Goldberg depression and anxiety scale, were used to analyze the effects of the SARS-Cov 2 outbreak after three months of mandatory social isolation. Analyses were performed by logistic regression and a clustering algorithm in order to classify subjects in the function of their outcome's severity. RESULTS: From 1059 surveys, the majority reported symptoms of depression (81.0%), anxiety (76.5%), poor sleep quality (84.7%), and insomnia (73.7%) with 58.9% suffering from nightmares. Logistic regression showed that being in contact with COVID-19 patients, age, gender and the consumption of sleep medication during the mandatory social isolation were relevant predictors for insomnia, anxiety, and depression. Clustering analysis classified healthcare workers in three groups with healthy/mild, moderate, and severe outcomes. The most vulnerable group was composed mainly of younger people, female, non-medical staff, or physicians in training. CONCLUSION: An extremely high proportion of Argentinian healthcare workers suffered from sleep problems, anxiety, and depression symptoms. The clustering algorithm successfully separates vulnerable from non-vulnerable populations suggesting the need to carry out future studies involving resilience and vulnerability factors.

Ten new cases of Balanced Reciprocal Translocation Mosaicism (BRTM): Reproductive implications, frequency and mechanism.

Chromosomal anomalies are well known to be an important cause of infertility, sterility and pregnancy loss. Balanced Reciprocal Translocation Mosaicism (BRTM) is an extremely rare phenomenon, mainly observed in subjects with a normal phenotype accompanied by reproductive failure. To date the mechanism of origin and the incidence of BRTM are poorly defined. Here we describe 10 new cases of BRTM. In 9 cases chromosome analysis revealed the presence of two different cell lines, one with a normal karyotype and the second with an apparently balanced reciprocal translocation. In the remaining case, both cell lines showed two different, but apparently balanced, reciprocal translocations. We document the clinical implications of BRTM, discuss its frequency in our referred population and suggest that carrier individuals might be more frequent than expected.

Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array-based detection rate.

BACKGROUND: Chromosomal microarray analysis (CMA) is nowadays widely used in the diagnostic path of patients with clinical phenotypes. However, there is no ascertained evidence to date on how to assemble single/combined clinical categories of developmental phenotypic findings to improve the array-based detection rate. METHODS: The Italian Society of Human Genetics coordinated a retrospective study which included CMA results of 5,110 Italian patients referred to 17 genetics laboratories for variable combined clinical phenotypes. RESULTS: Non-polymorphic copy number variants (CNVs) were identified in 1512 patients (30%) and 615 (32%) present in 552 patients (11%) were classified as pathogenic. CNVs were analysed according to type, size, inheritance pattern, distribution among chromosomes, and association to known syndromes. In addition, the evaluation of the detection rate of clinical subgroups of patients allowed to associate dysmorphisms and/or congenital malformations combined with any other single clinical sign to an increased detection rate, whereas non-syndromic neurodevelopmental signs and non-syndromic congenital malformations to a decreased detection rate. CONCLUSIONS: Our retrospective study resulted in confirming the high detection rate of CMA and indicated new clinical markers useful to optimize their inclusion in the diagnostic and rehabilitative path of patients with developmental phenotypes.

European guidelines for constitutional cytogenomic analysis.

With advancing technology and the consequent shift towards an increasing application of molecular genetic techniques (e.g., microarrays, next-generation sequencing) with the potential for higher resolution in specific contexts, as well as the application of combined testing strategies for the diagnosis of chromosomal disorders, it is crucial that cytogenetic/cytogenomic services keep up to date with technology and have documents that provide guidance in this constantly evolving scenario. These new guidelines therefore aim to provide an updated, practical and easily available document that will enable genetic laboratories to operate within acceptable standards and to maintain a quality service.

Generation of three iPSC lines (IAIi002, IAIi004, IAIi003) from Rubinstein-Taybi syndrome 1 patients carrying CREBBP non sense c.4435G>T, p.(Gly1479*) and c.3474G>A, p.(Trp1158*) and missense c.4627G>T, p.(Asp1543Tyr) mutations.

Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder characterized by growth retardation, skeletal anomalies and intellectual disability, caused by heterozygous mutations in either CREBBP (RSTS1) or EP300 (RSTS2) genes. We characterized 3 iPSC lines generated by Sendai from blood of RSTS1 patients with unique non sense c.4435G > T, p.(Gly1479*), c.3474G > A, p.(Trp1158*) and missense c.4627G > T, p.(Asp1543Tyr) CREBBP mutations. All lines displayed iPSC morphology, pluripotency markers, trilineage differentiation potential, stable karyotype and specific mutations. Western-blot using a CREB-Binding Protein N-terminus antibody demonstrated the same amount of full length protein as control in the missense mutation line and reduced amount in lines with stop mutations.

Genetics and mathematics: evidence from Prader-Willi syndrome.

Mathematical abilities were tested in people with Prader-Willi syndrome (PWS), using a series of basic mathematical tasks for which normative data are available. The difference between the deletion and the disomy variants of this condition was explored. While a wide phenotypic variation was found, some basic findings emerge clearly. As expected from previous literature, deletion and disomy participants were found to differ in their degree of impairment, with disomy being overall the most spared condition. However, the tasks selectively spared in the disomy condition are not necessarily the easiest ones and those that discriminate less the PWS group from controls. It rather seems that disomy patients are spared, with respect to deletion, in tasks entailing transcoding and comparison of numbers in the Arabic code. Overall a particular difficulty was detected in reliably performing parity judgments. This task has been shown to be very frequently spared after a brain injury, even in severe aphasic conditions. The most interesting result is the sparing in analog number scale, whereby PWS seem, overall, to outperform controls. This finding may help in understanding previously reported, surprising results about cognitive skills in PWS. Elevated performances in PWS may result from life-long hyper-reliance on one visuo-spatial system in presence of underdevelopment of the other.

The Italian National Survey for Prader-Willi syndrome: an epidemiologic study.

Twenty-five medical centers and the Prader-Willi Syndrome (PWS) Association collaborated on a study which attempted to identify all people with genetically confirmed diagnosis of PWS living in Italy. Investigators of the participating centers contacted PWS subjects and/or their family, filled in a specially developed form with the required data and forwarded this information by email. The study identified 425 subjects (209 males and 216 females, between the ages of 0.4-46.7). Two hundred thirty-eight patients had del15, 104 had UPD15, 4 demonstrated a translocation affecting chromosome 15 and 79 showed a positive methylation test. There were fewer subjects found over the age of 35, probably due to the low rate of identification of older PWS patients as well as the high mortality rate. There were a greater number of male children and adolescents with PWS whilst, amongst adults, there were more females. As expected, the majority of subjects with PWS were obese, especially in adult life. Nevertheless, it is noteworthy that 26% of patients aged between 6 and 17 were normal weight. A total of 212 subjects had received GH treatment, of which 141 were still receiving therapy, while the remaining 71 had stopped. In children and adolescents (233 cases), 89 subjects had never undergone GH therapy. Eighteen PWS patients had died in the past 20 years. Obesity-related cardiovascular and respiratory diseases were the cause of death, both during childhood and after 18 years of age. Three children died suddenly whilst undergoing GH therapy. Respiratory infection and cardiac illness were the causes of death in two cases. There was no definitive cause of death found in the third case. Overall, there was no increase in number of deaths during GH treatment, suggesting that GH administration in patients with PWS, as a group, does not increase the risk of death.

13q Deletion and central nervous system anomalies: further insights from karyotype-phenotype analyses of 14 patients.

BACKGROUND: Chromosome 13q deletion is associated with varying phenotypes, which seem to depend on the location of the deleted segment. Although various attempts have been made to link the 13q deletion intervals to distinct phenotypes, there is still no acknowledged consensus correlation between the monosomy of distinct 13q regions and specific clinical features. METHODS: 14 Italian patients carrying partial de novo 13q deletions were studied. Molecular-cytogenetic characterisation was carried out by means of array-comparative genomic hybridisation (array-CGH) or fluorescent in situ hybridisation (FISH). RESULTS: Our 14 patients showed mental retardation ranging from profound-severe to moderate-mild: eight had central nervous system (CNS) anomalies, including neural tube defects (NTDs), six had eye abnormalities, nine had facial dysmorphisms and 10 had hand or feet anomalies. The size of the deleted regions varied from 4.2 to 75.7 Mb. CONCLUSION: This study is the first systematic molecular characterisation of de novo 13q deletions, and offers a karyotype-phenotype correlation based on detailed clinical studies and molecular determinations of the deleted regions. Analyses confirm that patients lacking the 13q32 band are the most seriously affected, and critical intervals have been preliminarily assigned for CNS malformations. Dose-sensitive genes proximal to q33.2 may be involved in NTDs. The minimal deletion interval associated with the Dandy-Walker malformation (DWM) was narrowed to the 13q32.2-33.2 region, in which the ZIC2 and ZIC5 genes proposed as underlying various CNS malformations are mapped.

13q mosaic deletion including RB1 associated to mild phenotype and no cancer outcome - case report and review of the literature.

BACKGROUND: The 13q deletion syndrome is a rare chromosome disorder associated with wide phenotypic spectrum, which is related to size and location of the deleted region and includes intellectual disability, growth retardation, craniofacial dysmorphisms, congenital malformations, and increased risk of retinoblastoma. CASE PRESENTATION: Here, we report on a teenage boy with a mild phenotype characterized by obesity, hyperactivity, dysphagia, dysgraphia, sleep disturbance, and minor dysmorphic features (round face, bushy eyebrows, and stubby hands). Array Comparative Genomic Hybridization on blood identified a mosaic 13q14.13-13q31.1 deletion, with a mosaicism rate around 40%, which was confirmed by quantitative PCR and interphase Fluorescent In Situ Hybridization (iFISH) on both blood genomic DNA and cultured/uncultured blood lymphocytes, respectively. Conversely, karyotype analysis on blood estimated a mosaicism rate of 24% and iFISH on buccal smears revealed a borderline value of 0.4%, suggesting the absence of 13q deletion in this cell line. CONCLUSIONS: The comparison with previous patients carrying similar deletions informed that the proband clinical presentation is the mildest reported to date, thus supporting the burden of mosaicism in modulating the phenotype also in case of large chromosomal rearrangements. Characterization of further cases by in-depth mosaicism rate in tissues with different embryonic origins might contribute in the future to a better definition of genotype-phenotype correlation, including tumor risk.

Segmental Maternal UPD of Chromosome 7q in a Patient With Pendred and Silver Russell Syndromes-Like Features.

Pendred syndrome (PS) is an autosomal recessive disorder due to mutations in the SLC26A4 gene (chr7q22. 3) and characterized by sensorineural hearing loss and variable thyroid phenotype. Silver-Russell syndrome (SRS) is a heterogeneous imprinting disorder including severe intrauterine and postnatal growth retardation, and dysmorphic features. Maternal uniparental disomy of either the whole chromosome 7 (upd(7)mat) or 7q (upd(7q)mat) is one of the multiple mechanisms impacting the expression of imprinted genes in SRS, and is associated with milder clinical features. Here, we report genetic and clinical characterization of a female child with PS, postnatal growth retardation, and minor dysmorphic features. A gross homozygous deletion of SLC26A4 exons 17-20 was suspected by Sanger sequencing and then confirmed by array-CGH. Moreover, an insertion of about 1 kb of the CCDC126 gene (7p15.3), which does not appear to be clinically relevant, was detected. The possible occurrence of a balanced rearrangement between 7p and 7q was excluded. The absence of the deletion in the father led to the investigation of upd, and microsatellite segregation analysis revealed a segmental 7q (upd(7q)mat), leading to SLC26A4 homozygosity and responsible for both PS and SRS-like traits. The proband matched 3 out of 6 major SRS criteria. In conclusion, this is the first report of uniparental isodisomy encompassing almost the whole long arm of chromosome 7 resulting in PS and SRS-like features. Whereas, the inner ear phenotype of PS is typical, the clinical features suggestive of SRS might have been overlooked.

Generation of the Rubinstein-Taybi syndrome type 2 patient-derived induced pluripotent stem cell line (IAIi001-A) carrying the EP300 exon 23 stop mutation c.3829A > T, p.(Lys1277*).

Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder characterized by growth retardation, skeletal anomalies and intellectual disability, caused by heterozygous mutation in either the CREBBP (RSTS1) or EP300 (RSTS2) genes. We generated an induced pluripotent stem cell line from an RSTS2 patient's blood mononuclear cells by Sendai virus non integrative reprogramming method. The iPSC line (IAIi001RSTS2-65-A) displayed iPSC morphology, expressed pluripotency markers, possessed trilineage differentiation potential and was stable by karyotyping. Mutation and western blot analyses demonstrated in IAIi001RSTS2-65-A the patient's specific non sense mutation in exon 23 c.3829A > T, p.(Lys 1277*) and showed reduced quantity of wild type p300 protein.

Molecular cytogenetics characterization of seven small supernumerary marker chromosomes derived from chromosome 19: Genotype-phenotype correlation and review of the literature.

Only a few subjects carrying supernumerary marker chromosomes derived from 19 chromosome (sSMC(19)) have been described to date and for a small portion of them the genic content has been defined at the molecular level. We present seven new different sSMCs(19) identified in eight individuals, seven of whom unrelated. The presence of the sSMC is associated with a clinical phenotype in five subjects, while the other three carriers, two of whom related, are normal. All sSMCs(19) have been characterized by means of conventional and molecular cytogenetics. We compare the sSMCs(19) carriers with a clinical phenotype to already described patients with gains (sSMCs or microduplications) of overlapping genomic regions with the aim to deepen the pathogenicity of the encountered imbalances and to assess the role of the involved genes on the phenotype. The present work supports the correlation between the gain of some chromosome 19 critical regions and specific phenotypes.