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Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by deficiencies in communication, social interaction, and repetitive and restrictive behaviors. The discovery of genetic involvement in the etiology of ASD has made this condition a strong candidate for genome-based diagnostic tests. Next-generation sequencing (NGS) is useful for the detection of variants in the sequence of different genes in ASD patients. Herein, we present the implementation of a personalized NGS panel for autism (AutismSeq) for patients with essential ASD over a prospective period of four years in the clinical routine of a tertiary hospital. The cohort is composed of 48 individuals, older than 3 years, who met the DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders) diagnostic criteria for ASD. The NGS customized panel (AutismSeq) turned out to be a tool with good diagnostic efficacy in routine clinical care, where we detected 12 "pathogenic" (including pathogenic, likely pathogenic, and VUS (variant of uncertain significance) possibly pathogenic variations) in 11 individuals, and 11 VUS in 10 individuals, which had previously been negative for chromosomal microarray analysis and other previous genetic studies, such as karyotype, fragile-X, or MLPA/FISH (Multiplex Ligation dependent Probe Amplification/Fluorescence in situ hybridization) analysis. Our results demonstrate the high genetic and clinical heterogeneity of individuals with ASD and the current difficulty of molecular diagnosis. Our study also shows that an NGS-customized panel might be useful for diagnosing patients with essential/primary autism and that it is cost-effective for most genetic laboratories.

(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.

Autism spectrum disorders (ASD) comprise a group of neurodevelopmental disorders (NDD) characterized by deficits in communication and social interaction, as well as repetitive and restrictive behaviors, etc. The genetic implications of ASD have been widely documented, and numerous genes have been associated with it. The use of chromosomal microarray analysis (CMA) has proven to be a rapid and effective method for detecting both small and large deletions and duplications associated with ASD. In this article, we present the implementation of CMA as a first-tier test in our clinical laboratory for patients with primary ASD over a prospective period of four years. The cohort was composed of 212 individuals over 3 years of age, who met DSM-5 diagnostic criteria for ASD. The use of a customized array-CGH (comparative genomic hybridization) design (KaryoArray ® ) found 99 individuals (45.20%) with copy number variants (CNVs); 34 of them carried deletions (34.34%) and 65 duplications (65.65%). A total of 28 of 212 patients had pathogenic or likely pathogenic CNVs, representing approximately 13% of the cohort. In turn, 28 out of 212 (approximately 12%) had variants of uncertain clinical significance (VUS). Our findings involve clinically significant CNVs, known to cause ASD (syndromic and non-syndromic), and other CNVs previously related to other comorbidities such as epilepsy or intellectual disability (ID). Lastly, we observed new rearrangements that will enhance the information available and the collection of genes associated with this disorder. Our data also highlight that CMA could be very useful in diagnosing patients with essential/primary autism, and demonstrate the existence of substantial genetic and clinical heterogeneity in non-syndromic ASD individuals, underscoring the continued challenge for genetic laboratories in terms of its molecular diagnosis.

Chromosome-5p minus syndrome (5p-Sd, OMIM #123450) formerly known as Cri du Chat syndrome results from the loss of genetic material at the distal region of the short arm of chromosome 5. It is a neurodevelopmental disorder of genetic cause. So far, about 400 patients have been reported worldwide. Individuals affected by this syndrome have large phenotypic heterogeneity. However, a specific phenotype has emerged including global developmental delay, microcephaly, delayed speech, some dysmorphic features, and a characteristic and monochromatic high-pitch voice, resembling a cat's cry. We here describe a cohort of 70 patients with clinical features of 5p- Sd characterized by means of deep phenotyping, SNP arrays, and other genetic approaches. Individuals have a great clinical and molecular heterogeneity, which can be partially explained by the existence of additional significant genomic rearrangements in around 39% of cases. Thus, our data showed significant statistical differences between subpopulations (simple 5p deletions versus 5p deletions plus additional rearrangements) of the cohort. We also determined significant "functional" differences between male and female individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nevado, Bel-Fenellós, Sandoval-Talamantes, Hernández, Biencinto-López, Martínez-Fernández, Barrúz, Santos-Simarro, Mori-Álvarez, Mansilla, García-Santiago, Valcorba, Sáenz-Rico, Martínez-Frías and Lapunzina.)

Psoriasis is a chronic inflammatory disease with a multifactorial origin that affects the skin. It is characterized by keratinocyte hyperproliferation, which results in erythemato-squamous plaques. Just as the immune system plays a fundamental role in psoriasis physiopathology, the nervous system maintains the inflammatory process through the neuropeptides and neurotransmitters synthesis, as histamine, serotonin, calcitonin gene-related peptide, nerve growth factor, vasoactive intestinal peptide, substance P, adenosine, glucagon-like peptide, somatostatin and pituitary adenylate cyclase polypeptide. In patients with psoriasis, the systemic or in situ expression of these chemical mediators and their receptors are altered, which affects the clinical activity of patients due to its link to the immune system, provoking neurogenic inflammation. It is important to establish the role of the nervous system since it could represent a therapeutic alternative for psoriasis patients. The aim of this review is to offer a detailed review of the current literature about the neuropeptides and neurotransmitters involved in the physiopathology of psoriasis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: GATA2 mutations are associated with several conditions, including Emberger syndrome which is the association of primary lymphedema with hematological anomalies and an increased risk for myelodysplasia and leukemia., Objective: To describe a family with Emberger syndrome with incomplete penetrance., Methods: A DNA sequencing of GATA2 gene was performed in the parents and offspring (five individuals in total)., Results: The family consisted of 5 individuals with a GATA2 null mutation (c.130G>T, p.Glu44*); three of them were affected (two of which were deceased) while two remained unaffected at the age of 40 and 13 years old. The three affected siblings (two boys and one girl) presented with lymphedema of the lower limbs, recurrent warts, epistaxis and recurrent infections. Two died due to hematological abnormalities (AML and pancytopenia). In contrast, the two other family members who carry the same mutation (the mother and one brother) have not presented any symptoms and their blood tests remain normal., Discussion: Incomplete penetrance may indicate that GATA2 haploinsufficiency is not enough to produce the phenotype of Emberger syndrome. It could be useful to perform whole exome or genome sequencing, in cases where incomplete penetrance or high variable expressivity is described, in order to probably identify specific gene interactions that drastically modify the phenotype. In addition, skewed gene expression by an epigenetic mechanism of gene regulation should also be considered.

Background: Psoriasis is an autoimmune skin disease characterised by proliferation of keratinocytes, primarily due to cytokines Th1 and Th17. This profile is involved in pathogenesis of metabolic syndrome, a frequently found comorbidity in patients with psoriasis., Objective: In this study we determine the correlation of levels of pro-inflammatory cytokines TNF-α, IL-23, IL-12, and IL-22 in patients with psoriasis with and without metabolic syndrome and clinically healthy controls., Methods: We included 55 patients with plaque psoriasis: 30 with metabolic syndrome (PPMS), 25 without metabolic syndrome (PP), 15 healthy subjects (HS) and 15 with metabolic syndrome (MS). Quantification of serum levels of IL-12, TNF-α, IL-22, and IL-23 was done by ELISA., Results: We observed that serum levels of IL-12 were more elevated in PP group, while the lowest levels of TNF-α were seen in HS group. IL-22 was found to be higher in PP than in PPMS (p<0.05). PP patients with PASI scores rating as severe showed higher levels of IL-12. TNF-α level analysis showed significant differences in HS group compared with the others; levels of this cytokine were lower in patients with PP and moderate PASI scores than in MS group (p<0.05). We found no correlation between cytokine levels and psoriasis or between cytokines and PASI scores. In PP group, a positive correlation was observed between IL-23 and fasting glucose (r=0.432, p<0.05), as well as a negative correlation between IL-23, IL-22, and IL-12 versus waist circumference (r=-0.504, r=-0.556 and r=-0.511, respectively; p<0.05)., Conclusions: Psoriasis is not just a skin disorder, but rather a condition with systemic implications, with intervention of pro-inflammatory cytokines that contribute to metabolic syndrome and other comorbidities, which in turn increases the risk of developing cardiovascular disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The aim of our study was to determine the frequency and type of associated congenital anomalies in patients with isolated gastroschisis born at the Dr. Juan I. Menchaca Civil Hospital of Guadalajara (Guadalajara, México), and to explore its possible association with the included outcome variables. One hundred-eight cases with isolated gastroschisis were reviewed from 2009 to 2014. The occurrence of intestinal and extraintestinal associated anomalies (either secondary or primary) was prospectively assessed. The type of gastroschisis, length of hospital stay (LOS), and in-hospital mortality were outcome variables for statistical analysis. Of infants with gastroschisis, 52 (48.1%) had one or more associated anomalies (AA), with increased odds in males (OR = 2.3, 95%CI: 1.1-5.0). AA classified, as secondary and primary were present in 34.3 and 5.6% of patients, respectively. Of secondary AA, 25.9% were intestinal anomalies, and 17.6% were extraintestinal. Primary AA were congenital heart disease (n = 3), meningomyelocele, and hydrocephaly and amniotic band sequence in one instance, respectively. Multivariate logistic regression showed that secondary AA (both intestinal and extraintestinal) were associated with complex gastroschisis, prolonged LOS, and in-hospital death, whereas primary AA were not related to a worse outcome. Our results highlight the pathogenic importance of properly investigating and categorizing the presence of others secondary or primary AA when diagnosis of gastroschisis is made., (© 2015 Wiley Periodicals, Inc.)

Psoriasis is a chronic autoimmune inflammatory disease that affects the skin and the joints. Psoriasis is characterized by the keratinocyte proliferation, which is induced by cytokines Th1 and Th17. Patients with plaque psoriasis present a chronic inflammatory response with high levels of interleukin (IL)-12 and IL-23. Various single-nucleotide polymorphisms (SNP) have been identified in the IL12B gene, such as SNP 3' UTR 1188 A/C (SNP rs3212227), which has been associated with susceptibility to developing plaque psoriasis and with the production of IL-12 and IL-23 in individuals of different ethnic groups. In this study, we determined whether there is an association of SNP rs3212227 with the susceptibility of developing plaque psoriasis and with serum levels of IL-12 and IL-23 in Mestizo population in western Mexico. We included 112 patients with psoriasis and 112 clinical healthy individuals in the study. The frequencies of genotypes A/A, A/C, and C/C in patients with plaque psoriasis were 41, 53, and 6%, respectively, while in the control group, these were 37, 53, and 10%, respectively, without finding statistically significant differences between both groups (p>0.05). Although IL-12 and IL-23 serum levels were higher in patients than in controls, we found no significant differences. The group of patients with genotype CC presented the highest levels of IL-23 (p<0.05). These data suggest that the SNP rs3212227 phenotype is not associated with the risk of developing plaque psoriasis or with IL-12 and IL-23 levels in Mestizo population in western Mexico., (Copyright © 2014 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)