Search results for "Dysgenesis"
showing 10 items of 24 documents
Two Cases of Thyroid Dysgenesis Caused by Different Novel PAX8 Mutations in the DNA-Binding Region: In Vitro Studies Reveal Different Pathogenic Mech…
2013
Mutations in PAX8, a transcription factor gene, cause thyroid dysgenesis (TD). The extreme variability of the thyroid phenotype makes it difficult to identify individuals harboring PAX8 gene mutations. Here we describe two patients with TD and report two novel PAX8 gene mutations (S54R and R133Q). We performed in vitro studies to functionally characterize these mutations.Using PAX8 expression vectors, we investigated whether the PAX8 mutants localized correctly to the nucleus. To analyze the DNA-binding properties of S54R and R133Q, electrophoretic mobility shift assays were performed. Furthermore, we measured whether the mutant PAX8 proteins were able to activate the thyroglobulin (TG)- an…
Mutations in the NKX2.1 and the PAX8 genes in a boy with thyroid dysgenesis, respiratory and neurological disorders
2015
s of the 51st Workshop for Pediatric Research 51st Workshop for Pediatric Research Gottingen, Germany
Sperm imprinting integrity in seminoma patients?
2018
IF 4.990; International audience; BackgroundTesticular germ cell tumor such as seminoma is strongly associated with male reproductive problems commonly associated with the alteration of sperm parameters as described in testicular dysgenesis syndrome. Interestingly, numerous studies have reported that the precursor of germ cell cancer, germ cell neoplasia in situ (GCNIS), present similarities to fetal gonocytes, specifically characterized by global DNA hypomethylation particularly on imprinting sequences. These disorders may have a common origin derived from perturbations of embryonal programming during fetal development. Presently, there is no available information concerning the sperm DNA …
Congenital hypothyroidism: A 2020-2021 consensus guidelines update-An ENDO-European Reference Network initiative endorsed by the European Society for…
2021
Background: An ENDO-European Reference Network (ERN) initiative was launched that was endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology with 22 participants from the ENDO-ERN and the two societies. The aim was to update the practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). A systematic literature search was conducted to identify key articles on neonatal screening, diagnosis, and management of primary and central CH. The evidence-based guidelines were graded with the Grading of Recommendations, Assessment, Development and Evaluation system, describing both the strength of recommendations and the quali…
Developmental Abnormalities of the Thyroid
2016
Developmental anomalies of the thyroid gland (thyroid dysgenesis) underlie the majority of cases of congenital hypothyroidism. Only a small number of monogenic defects have been shown to result in athyreosis or orthotopic thyroid hyperplasia, whereas the commonest developmental anomaly, thyroid ectopy, remains unexplained. Ectopy may result from multiple genetic or epigenetic hits in the germline and/or at the somatic level. This chapter gives a brief overview of the monogenic defects in candidate genes that have been identified so far and of the syndromes that are known to be associated with thyroid dysgenesis. In addition, we discuss gain-of-function mutations of the thyroid hormone stimu…
Developmental Abnormalities of the Thyroid
2010
Publisher Summary This chapter explores the abnormalities in the development of the thyroid gland during organogenesis referred to as thyroid dysgenesis. Permanent primary congenital hypothyroidism (CH) is mentioned to be the most common congenital endocrine disorder as estimated from systematic biochemical screening of newborns. The functional disorders of the thyroid gland are known as thyroid dyshormonogenesis and this disorder is typically inherited in an autosomal recessive manner and common in populations with a high degree of consanguinity. It briefly reviews the single gene disorders that cause CH from thyroid dysgenesis, and mutations that activate the thyrotropin receptor (TSH) re…
Absence of mutations in the WT1 gene in patients with XY gonadal dysgenesis
1995
The WT1 gene is normally expressed during gonadal development and specific mutations in heterozygous form cause Drash syndrome, characterized by male pseudohermaphroditism and gonadal dysgenesis, renal failure and a predisposition for Wilms' tumour. These observations prompted us to test whether WT1 mutations are involved in isolated gonadal dysgenesis, being the most severe form of disturbance in gonadal differentiation. We studied 27 cases of 46,XY females with gonadal dysgenesis who had previously been screened for and found not to carry SRY gene mutations. We performed mutational screening of the WT1 gene with denaturing gradient gel electrophoresis. In one of these patients, a heterozy…
A New Mutation in the Promoter Region of the PAX8 Gene Causes True Congenital Hypothyroidism with Thyroid Hypoplasia in a Girl with Down's Syndrome
2014
Thyroid dysfunction is common in newborn infants with Down's syndrome (DS), but defects causing classic thyroid dysgenesis (TD) with permanent congenital hypothyroidism (CH) have not been described.We studied a girl with DS and CH who had a mutation in the promoter sequence of the PAX8 gene.A female infant was found to have trisomy 21 and CH, with a venous thyrotropin (TSH) of150 mU/L and a free thyroxine (fT4) of 15.1 pmol/L (day 12). Thyroid peroxidase antibodies and thyroglobulin antibodies were elevated. Scintigraphy showed normal uptake, but ultrasound identified a small gland with heterogenous echotexture and cystic changes. Sequence analysis of the PAX8 gene revealed a new heterozygo…
Hybridization, developmental stability, and functionality of morphological traits in the ground beetle Carabus solieri (Coleoptera, Carabidae).
2006
Correspondance.: stephane.garnier@u-bourgogne.fr; International audience; The assessment of developmental stability in hybrids can provide valuable information in the study of species formation because it allows an evaluation of the degree of incompatibility of genetic systems that control developmental processes. The present study assessed the impact of two hybridization events, assumed to have occurred at different times, on developmental instability in the ground beetle Carabus solieri . Developmental instability was estimated in 678 individuals from 27 populations from the fluctuating asymmetry (FA) levels of four morphological traits: the tibia length of middle and hind legs, which are…
Motor problems in children with early-treated congenital hypothyroidism: A matter of failing cerebellar motor control?
1998
This study addresses the question of whether "clumsiness" in children with early treated Congenital Hypothyroidism (CH) might be attributable to cerebellar dysfunction. CH is known to affect rapid perinatal growth of the cerebellum. If this would affect the supposed motor timing function of the cerebellum this should be especially reflected by difficulty in producing fast aiming movements. An experiment was devised in which children made sequences of fast, goal directed movements in order to examine two aspects of fast voluntary movements that are known to be affected by cerebellar injury: dysmetria and dysdiadochokinesis. Three groups of children between the ages of 9 and ii participated: …