Clinical and genetic aspects of Turner’s syndrome

Turner’s syndrome, or monosomy X, is defined as the total or partial loss of the second sex chromosome. The clinical phenotype is highly variable and includes short stature, gonadal dysgenesis, pterygium colli, cubitus valgus and low hairline. The variable expressivity of height and other physical features may be only partially related to the chromosomal formula. Currently, the delay in the diagnosis of Turner’s syndrome remains a problem, as only 15---30% of patients are diagnosed during their first year of life. Understanding its complex etiology and learning more about its clinical variability and complications will allow us to advance the therapeutic and management approach of such patients. This review summarizes the clinical characteristics of, and diagnostic tests for, Turner’s syndrome and the advances in the study of its underlying genetic factor

Expression profile of microRNAs in the testes of patients with Klinefelter syndrome

Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy. A distinctive characteristic of KS is oligozoospermia. Despite multiple studies that have described the natural history of the degenerative process of germ cells in patients with KS, the molecular mechanisms that initiate this process are not well characterized. MicroRNA (miRNA)-mediated post-transcriptional control mechanisms have been increasingly recognized as important regulators of spermatogenesis; however, only a few studies have evaluated the role of miRNAs in the gonadal failure of these patients. Here, we describe a differential expression profile for the miRNAs in testicular tissue samples taken from KS patients. We analysed testicular tissue samples from 4 KS patients and 5 control patients (obstructive azoospermia) through next-generation sequencing, which can provide information about the mechanisms involved in the degeneration of germ cells. A distinctive differential expression profile was identified for 166 miRNAs in the KS patients: 66 were upregulated, and 100 were downregulated. An interactome analysis was performed for 7 of the upregulated and the 20 downregulated miRNAs. The results showed that the target genes are involved in the development, proliferation, and differentiation processes of spermatogenesis, which may explain their role in the development of infertility. This is the first report of a miRNA expression profile generated from testicular tissue samples of KS patients

Spondylothoracic dysostosis, Jarcho Levin syndrome: case report

Dysostosis spondylothoracic, or Jarcho Levin syndrome, is characterized by a short neck and thorax, a protruding abdomen, abnormal vertebral segmentation and fusion posterior costal resulting in thoracic restriction or respiratory failure and scoliosis. The prevalence is estimated at 1 in 12,000 live births for the people of Puerto Rico and 1 per 200,000 for the rest of the world. It is inherited in an autosomal recessive manner and the only related gene is MESP2. Clinical case: Newborn male, who during the first hour of life develops perioral cyanosis, thoracoabdominal dissociation and polipnea, requiring endotracheal intubation and mechanical ventilation for respiratory impairment, finding thoracoabdominal costovertebral abnormalities with an x-ray, and a conditioning restrictive pattern like a crab. During the physical examination, we found horizontal eyelid openings, right atrial appendage, straight nasal bridge, short thorax and asymmetry and hypertrichosis, predominantly in the back. A diagnosis of dysostosis spondylothoracic is confirmed, and the patient was discharged at 7 days of age, with follow up neonatal consultation at high risk

Consulta génetica y asesoramiento

El asesoramiento genético consiste en brindar información verdadera, íntegra y objetiva en una relación de atención profesional que proporciona orientación que permite a los pacientes y sus familias tomar decisiones informadas, con respeto a su autonomía. El asesoramiento genético es fundamental no solamente para el diagnóstico sino también previo a efectuar cualquier prueba genética y debe proseguir después si los resultados comprenden alternativas para el individuo y la familia. El asesoramiento debe estar al alcance de todos y no debe confundirse con aconsejar

Detection of Turner Syndrome by Quantitative PCR of SHOX and VAMP7 Genes

Turner Syndrome (TS) is an unfavorable genetic condition with a prevalence of 1:2500 in newborn girls. Prompt and effective diagnosis is very important to appropriately monitor the comorbidities. The aim of the present study was to propose a feasible and practical molecular diagnostic tool for newborn screening by quantifying the gene dosage of the SHOX, VAMP7, XIST, UBA1, and SRY genes by quantitative polymerase chain reaction (qPCR) in individuals with a diagnosis of complete X monosomy, as well as those with TS variants, and then compare the results to controls without chromosomal abnormalities. According to our results, the most useful markers for these chromosomal variants were the genes found in the pseudoautosomic regions 1 and 2 (PAR1 and PAR2), because differences in gene dosage (relative quantification) between groups were more evident in SHOX and VAMP7 gene expression. Therefore, we conclude that these markers are useful for early detection in aneuploidies involving sex chromosomes

Unexpected reactivity of “GaI” towards N,N′-diaryl-β-diketiminate tin(II) chloride: Synthesis, X-ray diffraction analysis and DFT studies

Reaction of the [HC(CMeNAr)2]SnCl (Ar = 2,4,6-Me3C6H2) with ‘‘GaI” in THF provided an unexpected transhalogenation reaction product [HC(CMeNAr)2]SnI. The crystal structure shows a tin(II) ion with a distorted tetrahedral pyramidal geometry. Theoretical calculations, using density functional theory (B3LYP), suggest the probable reaction mechanism for transhalogenation. The activation energy for moving from reactant ([HC(CMeNAr)2]SnCl to product [HC (CMeNAr)2]SnI) is only 10.2 kcal/mol. The chloride ion is displaced by the iodine ion, probably by the help of the gallium atom when it is coordinated to the chlorine atom

Gene Copy Number Quantification of SHOX , VAMP7 , and SRY for the Detection of Sex Chromosome Aneuploidies in Neonates

Aims: To explore the feasibility of detecting sex chromosome aneuploidies (SCAs) by means of gene copy number quantification of short stature homeobox (SHOX), vesicle-associated membrane protein 7 (VAMP7), and SRY in newborns. Materials and Methods: Gene doses of SHOX, VAMP7, and SRY were determined by quantitative polymerase chain reaction (qPCR) using DNA obtained from dried blood samples from newborns. Relative quantification values were obtained. An aneuploidy profile was established according to cutoff values. Samples with ≥2 gene doses (out of range) were reanalyzed, and those with aneuploidy profiles were confirmed by karyotyping. Sensitivity, specificity, and positive and negative predictive values were obtained. Results: A total of 10,033 samples were collected (4945 females and 5088 males). Of 244 (2.43%) samples with ≥2 gene doses that were retested, 20 cases were confirmed. The overall incidence of SCAs was 1 in 500 live newborns. There were six cases of Turner syndrome (1/824), 3 cases of XXX (1/1648), 7 cases of Klinefelter syndrome (1/726), and 4 cases of of XYY (1/1272). The sensitivity was 0.952 (95.24%), specificity of 0.975 (97.56%), positive predictive value of 0.909 (90.91%), and negative predictive value of 0.987 (98.77%). Conclusions: Gene copy number analyses of VAMP7, SHOX, and SRY genes by qPCR from blood samples spotted onto filter paper is a highly reliable method for the early detection of male and female SCAs

Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies

Ciencia Odontológica 2.0

Libro que muestra avances de la Investigación Odontológica en MéxicoEs para los integrantes de la Red de Investigación en Estomatología (RIE) una enorme alegría presentar el segundo de una serie de 6 libros sobre casos clínicos, revisiones de la literatura e investigaciones. La RIE está integrada por cuerpos académicos de la UAEH, UAEM, UAC y UdeG