hes1-protein--human and Congenital-Hypothyroidism

To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis.. Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development.. No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (78%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001).. Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.

Topics: Brazil; Child, Preschool; Cohort Studies; Congenital Hypothyroidism; DNA Mutational Analysis; Female; Genetic Testing; Homeobox Protein Nkx-2.5; Humans; Infant; Infant, Newborn; Male; Mutation; Neonatal Screening; PAX8 Transcription Factor; Receptors, Thyrotropin; Thyroid Dysgenesis; Thyrotropin; Thyroxine; Transcription Factor HES-1; Ultrasonography

Permanent primary congenital hypothyroidism (CH) can be caused by abnormal thyroid differentiation (athyreosis), migration (ectopy), or function (leading to goiter). Goiters follow an autosomal recessive pattern of inheritance, whereas ectopy and athyreosis are considered as a single sporadic entity with a female preponderance. On the other hand, a high prevalence of extrathyroidal malformations has been reported in CH, but without linking specific defects to specific types of CH. On the basis of TSH screening, 273 newborns were referred to an academic pediatric endocrinology clinic in the province of Quebec between 1988 and 1997. Of 230 patients with permanent primary CH who had scintigraphy at diagnosis, 141 had ectopy (104 girls), 36 had athyreosis (21 girls), 42 had goiter (18 girls), 10 (3 girls) had a normal scan, and 1 girl had hemiagenesis. Only in the ectopies was the proportion of girls significantly higher than 0.5 (P<0.001). Isolated cardiac malformations were observed in 7 patients (3.0%), a prevalence 5-fold higher than that in the general population; this was largely due to atrial and ventricular septal defects, which were only observed in ectopy and athyreosis. Our data suggest that the molecular mechanisms that lead to complete absence of thyroid differentiation or defective thyroid migration 1) may be similar, but are modulated by the genetic makeup of the embryo and/or the hormonal milieu of the fetus; and 2) may also be involved in septation of the embryonic heart.

Topics: Abnormalities, Multiple; Basic Helix-Loop-Helix Transcription Factors; Congenital Hypothyroidism; DNA-Binding Proteins; Female; Forkhead Transcription Factors; Homeodomain Proteins; Humans; Hypothyroidism; Infant, Newborn; Male; Mutation; Nuclear Proteins; Paired Box Transcription Factors; PAX8 Transcription Factor; Radionuclide Imaging; Repressor Proteins; Sex Characteristics; Thyroid Gland; Thyroid Hormones; Trans-Activators; Transcription Factor HES-1