Explore the vast range of titles available.

Objective5p deletion syndrome, that characterized by cat-like cry and peculiar timbre of voice, is believed to be one of the most common pathogenic copy number variations (CNVs). Variable critical regions on 5p involving a variety of genes contribute to the phenotypic heterogeneity without specific correlation. The objective of this study was to examine the genotype–phenotype correlation of 5p deletion syndrome, and to redefine 5p deletion syndrome relevant regions. In addition, we demonstrate the potential use of whole genome sequencing (WGS) to identify chromosomal breakpoints in prenatal diagnosis.MethodsThree families with women undergoing prenatal diagnosis and two children were recruited. Karyotyping, CNV-seq, fluorescence in situ hybridization, WGS, and Sanger sequencing were performed to identify the chromosomal disorder.ResultsWe reported three families and two children with CNVs of 5p deletion or combined 6p duplication. Five different sizes of 5p deletion were detected and their pathogenicity was determined, including 5p15.33-p15.31 [1–7,700,000, family1-variant of uncertain significance (VUS)], 5p15.33 (1–3,220,000, family 2-VUS), 5p15.33-p15.31 (1–7,040,000, family 3-VUS), 5p15.33-p15.31 (1–8,740,000, child 1-pathogenic) and 5p15.31-p15.1 (8,520,001–18,080,000, child 2-pathogenic). One duplication at 6p25.3-p24.3 (1–10,420,000) was detected and determined as likely pathogenic. The chromosomal breakpoints in family 3 were successfully identified by WGS.ConclusionSome critical genes that were supposed to be causative of the symptoms were identified. Relevant region in 5p deletion syndrome was redefined, and the chr5:7,700,000–8,740,000 region was supposed to be responsible for the cat-like cry. The great potential of WGS in detecting chromosomal translocations was demonstrated. Our findings may pave the way for further research on the prevention, diagnosis, and treatment of related diseases.

The cri-du-chat syndrome is caused by a deletion on the short arm of chromosome number 5. The size of genetic material loss varies from the 5p15.2 region only to the whole arm. Prevalence rates range between 1:15000 and 1:50000 live births. Diagnosis is suspected on infants with a high-pitched (cat-like) cry, facial dysmorfism, hypotonia and delayed psychomotor development. In adults, phenotypic findings are less specific. It is confirmed through high-resolution G-banding karyotype, fluorescent in situ hybridization or microarray-based comparative genomic hybridization (a-CGH). The following is the case report of a 21-year-old female patient with severe mental retardation and trichotillomania, who does not control sphincters and does not bathe or eat by herself. Her communication is based only on sounds and dysmorphic facies. The G-band karyotype reported is 46, XX. a-CGH shows 18.583Mb interstitial microdeletion in 5p15.33p14.3, including the cri-du-chat critical region. In children or adults with unexplained mental retardation and normal karyotype results (like this case), an a-CGH should be performed to make an etiological diagnosis, establish the prognosis, order additional medical tests and specific treatments, and offer appropriate genetic counseling.

The Cri Du Chat (CdC) Syndrome is a rare chromosome disease condition resulting from variable size deletion occurring on the short arm of one of the chromosomes 5. This disorder, which affects one in 50,000 births, is responsible for developmental retardation, the mechanism of which has remained unexplained. TERT, SEMA5 A, CTNND2, TPPP, mapped in chromosome 5 short arm, are known to be expressed in the brain, and to play a role in the development of the nervous system, oligodentrocytes and in the regulation of glutamatergic and dopaminergic synaptic transmission. It is critical to understand how their haploinsufficiency might affect the development and presentation of the disease. In the absence of an animal model and of significant accessible, human tissue, human pluripotent stem cells (iPSC) directly reprogrammed from patient somatic cells open a new area of disease modeling as they can virtually be differentiated into any cell type. Our study reports, for the first time, the generation of neuronal stem cells (NSCs) from CdC-iPSCs line and in addition, subsequent differentiation into a heterogeneous population of neurons. Gene expression of the mentioned and single copy deleted genes was also evaluated by comparing their expression level in iPSC, NSCs and neuron lines. The present research represents the first and the most innovative approach, to create an in vitro CdC neuronal model to have a new translational framework to study the pathologic processes.

(1) Background: 5p minus Syndrome (S5p-) is a neurodevelopmental disorder caused by a deletion in the short arm of chromosome 5. Among the phenotypic characteristics of S5p-, the most characteristic and representative element is a monochromatic cry with a high-pitched tone reminiscent of a cat’s meow. Individuals may also show great phenotypic heterogeneity and great genetic variability. Regarding cognitive–behavioral aspects of the syndrome, the studies are scarce and do not establish a general profile of the main cognitive–behavioral particularities that this syndrome presents. The main objective of this work was to describe the development profile of a cohort of 45 children with 5p minus Syndrome, concerning the biomedical, genetic, cognitive, and behavioral aspects. Establishing putative genotype–phenotype (cognitive–behavioral profiles) relationships in our cohort, from an interdisciplinary approach. (2) Methods: A selection of instruments of measures was selected for neuropsychological assessment (3) Results: In general, children with S5p- have a higher cognitive level than a communicative and motor level. Language difficulties, especially expressive ones, influence the frequency and severity of the most frequent behavioral problems in S5p. The most significant problem behavior of children with S5p-, especially girls, is self-harm. Compulsive behavior, limited preferences, and interest in monotony are significantly more frequent in subjects with better cognitive levels. We also find a significant correlation between the size of the loss of genetic material on 5p and the cognitive level of the subjects. (4) Conclusions: We described for the first time, the cognitive–behavioral profile of a cohort of minors with S5p-. Remarkably, it was found that language, especially of an expressive nature, modulates the most frequent behavioral aspects in subjects with lower cognitive levels, so it is essential to develop verbal or alternative communication strategies adjusted to these individuals.

Background This study aimed to define the molecular basis for 12 prenatal cases of Cri‐du‐chat syndrome (CdCS) and the potential genotyping‐phenotyping association. Methods Karyotyping and single nucleotide polymorphism array analyses for copy number variants were performed. Results Nine cases had 5p terminal deletions and three had 5p interstitial deletions, and these cases had variable deletion sizes with partial overlapping. Phenotypically, besides intrauterine growth restriction (IUGR) and brain as well as heart abnormalities, hypospadias, and lung dysplasia were observed. Potential genetic causes for specific phenotypes in these cases were identified. Conclusion This study defined the molecular bases for the patients of CdCS, which is important for genetic counseling for these families. The findings of present study expand the clinical features of CdCS in the fetal period, and provided important information for further refining the genotypic–phenotypic correlations for this syndrome. This study provides clinical and molecular characterization for 12 prenatal case of Cri‐du‐chat syndrome (CdCS) and genotyping‐phenotyping analysis for these cases. The findings from the present study are important for genetic counseling for the families of affected individuals, expand the clinical features of CdCS in the fetal period, and provide important information for further refining the genotypic–phenotypic correlations for this syndrome.

Background Rearrangements involving chromosome 5p often result in two syndromes, Cri-du-chat (CdC) and Trisomy 5p, caused by a deletion and duplication, respectively. The 5p15.2 has been defined as a critical region for CdC syndrome; however, genotype-phenotype studies allowed isolation of particular characteristics such as speech delay, cat-like cry and mental retardation, caused by distinct deletions of 5p. A varied clinical outcome was also observed in patients with Trisomy 5p. Duplications of 5p10-5p13.1 manifest themselves in a more severe phenotype, while trisomy of regions distal to 5p13 mainly causes mild and indistinct features. Combinations of a terminal deletion and inverted duplication of 5p are infrequent in literature. Consequences of these chromosomal rearrangements differ, depending on size of deletion and duplication in particular cases, although authors mainly describe the deletion as the cause of the observed clinical picture. Case presentation Here we present a 5-month-old Slovenian girl, with de novo terminal deletion and inverted duplication of chromosome 5p. Our patient presents features of both CdC and Trisomy 5. The most prominent features observed in our patient are a cat-like cry and severe malformations of the right ear. Conclusion The cat-like cry, characteristic of CdC syndrome, is noted in our patient despite the fact that the deletion is not fully consistent with previously defined cat-like cry critical region in this syndrome. Features like dolichocephaly, macrocephaly and ear malformations, associated with duplication of the critical region of Trisomy 5p, are also present, although this region has not been rearranged in our case. Therefore, the true meaning of the described chromosomal rearrangements is discussed.

Background Carriers of balanced reciprocal chromosomal translocations are at known reproductive risk for offspring with unbalanced genotypes and resultantly abnormal phenotypes. Once fertilization of a balanced translocation gamete with a normal gamete, the partial monosomy or partial trisomy embryo will undergo abortion, fetal arrest or fetal malformations. We reported a woman with chromosomal balanced translocation who had two adverse pregnancies. Prenatal diagnosis was made for her third pregnancy to provide genetic counseling and guide her fertility. Case presentation We presented a woman with chromosomal balanced translocation who had three adverse pregnancies. Routine G banding and CNV-seq were used to analyze the chromosome karyotypes and copy number variants of amniotic fluid cells and peripheral blood. The karyotype of the woman was 46,XX,t(4;5)(q33;p15). During her first pregnancy, odinopoeia was performed due to fetal edema and abdominal fluid. The umbilical cord tissue of the fetus was examined by CNV-seq. The results showed a genomic gain of 24.18 Mb at 4q32.3-q35.2 and a genomic deletion of 10.84 Mb at 5p15.2-p15.33 and 2.36 Mb at 15q11.1-q11.2. During her second pregnancy, she did not receive a prenatal diagnosis because a routine prenatal ultrasound examination found no abnormalities. In 2016, she gave birth to a boy. The karyotype the of the boy was 46,XY,der(5)t(4;5)(q33;p15)mat. The results of CNV-seq showed a deletion of short arm of chromosome 5 capturing regions 5p15.2-p15.33, a copy gain of the distal region of chromosome 4 at segment 4q32.3q35.2, a duplication of chromosome 1 at segment 1q41q42.11 and a duplication of chromosome 17 at segment 17p12. During her third pregnancy, she underwent amniocentesis at 17 weeks of gestation. Chromosome karyotype hinted 46,XY,der(5)t(4;5)(q33;p15)mat. Results of CNV-seq showed a deletion of short arm (p) of chromosome 5 at the segment 5p15.2p15.33 and a duplication of the distal region of chromosome 4 at segment 4q32.3q35.2. Conclusions Chromosomal abnormalities in three pregnancies were inherited from the mother. Preimplantation genetic diagnosis is recommended to prevent the birth of children with chromosomal abnormalities.

The majority of deletions of the short arm of chromosome 5 are associated with cri du chat syndrome (CdCS) and patients show phenotypic and cytogenetic variability. To perform a genotype-phenotype correlation, 80 patients from the Italian CdCS Register were analysed. Molecular cytogenetic analysis showed that 62 patients (77.50%) had a 5p terminal deletion characterised by breakpoint intervals ranging from p13 (D5S763) to p15.2 (D5S18). Seven patients (8.75%) had a 5p interstitial deletion, four (5%) a de novo translocation, and three (3.75%) a familial translocation. Of the remaining four patients, three (3.75%) had de novo 5p anomalies involving two rearranged cell lines and one (1.25%) had a 5p deletion originating from a paternal inversion. The origin of the deleted chromosome 5 was paternal in 55 out of 61 patients (90.2%). Genotype-phenotype correlation in 62 patients with terminal deletions highlighted a progressive severity of clinical manifestation and psychomotor retardation related to the size of the deletion. The analysis of seven patients with interstitial deletions and one with a small terminal deletion confirmed the existence of two critical regions, one for dysmorphism and mental retardation in p15.2 and the other for the cat cry in p15.3. Results from one patient permitted the cat cry region to be distally narrowed from D5S13 to D5S731. Furthermore, this study lends support to the hypothesis of a separate region in p15.3 for the speech delay.

ObjectiveTo find the length and location of the deletions in the short arm of chromosome 5 in one case of Cri du Chat syndrome using oligo array comparative genomic hybridization.MethodsMetaphase chromosomes were prepared from peripheral blood lymphocyte cultures using standard cytogenetic protocols. Chromosomal analysis was done in G-banded metaphases. Oligo array comparative genomic hybridization and fluorescence in situ hybridization were performed by the commercially available kits.ResultsOligonucleotide array comparative genomic hybridization (CGH) analysis revealed a 23.263 Mb deletion at region 5p14.2-->qter, combined with a duplication of 14.602 Mb in size in the area 12p13.1-->pter. Chromosomal aberrations were confirmed by fluorescence in situ hybridization. The male neonate with Cri du Chat syndrome had an unbalanced translocation which was inherited from his father who was a balanced carrier with a karyotype 46, XY, t (5; 12) (p14.2; p13.1).ConclusionsThis report shows the clinical utility of the oligonucleotide array in the detection of submicroscopic chromosomal aberrations, thus improving the molecular diagnosis of Cri du Chat syndrome.

We report on a preterm neonate with a deletion of the distal short arm of chromosome 5p15.33 and partial trisomy of the distal short arm of chromosome 3p24.3. The patient was the first-born monozygotic twin. There were no pertinent facial or physical features except a small lower lip hemangioma. The neonate presented with cardiac defects, which included a patent ductus arteriosus, an atrial septal defect and ventricular septal defects. After 94 days of age, however, the patient died from superior vena cava syndrome, recurrent chylothoraces and generalized anasarca. Array comparative genomic hybridization (aCGH) using a custom oligonucleotide microarray (Agilent 180,000 probe platform revealed a terminal duplication of 1,128 oligonucleotide probes from 3pter to 3p24.3, spanning approximately 20.4 megabases (Mb), and a terminal deletion of 271 oligonucleotide probes from 5pter to 5p15.33, spanning approximately 4.3 Mb. This is the first report of a patient with partial trisomy 3p24.3 and partial monosomy 5p15.33 without major dysmorphic features.