Molecular analysis of PAX8 gene in unrelated patients with congenital hypothyroidism

10.5580/a01 ◽  
2007 ◽  
Vol 3 (2) ◽  
Keyword(s):  
Molecular Analysis ◽  
Congenital Hypothyroidism ◽  
Pax8 Gene

Molecular analysis of the PAX8 gene in a sample of Mexican patients with primary congenital hypothyroidism: identification of the recurrent p.Arg31His mutation

2011 ◽  
Vol 76 (1) ◽  
pp. 148-150 ◽  
Author(s):  
Miguel Angel Alcántara-Ortigoza ◽  
Ariadna González-del Angel ◽  
Víctor Martínez-Cruz ◽  
Marcela Vela-Amieva ◽  
Carmen Sánchez-Pérez ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Congenital Hypothyroidism ◽  
Pax8 Gene ◽  
Mexican Patients

scholarly journals 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

Thyroid ◽  
2014 ◽  
Vol 24 (6) ◽  
pp. 939-944 ◽  
Author(s):  
Pia Hermanns ◽  
Scott Shepherd ◽  
Mohamed Mansor ◽  
John Schulga ◽  
Jez Jones ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Promoter Region ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
New Mutation ◽  
Pax8 Gene

scholarly journals Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations

2014 ◽  
Vol 171 (4) ◽  
pp. 499-507 ◽  
Author(s):  
H E Ramos ◽  
A Carré ◽  
L Chevrier ◽  
G Szinnai ◽  
E Tron ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Screening Program ◽  
Phenotypic Variability ◽  
Cross Sectional Study ◽  
The Novel ◽  
Loss Of Function ◽  
Cross Sectional ◽  
Clinical Presentations ◽  
Pax8 Gene

ContextWithin the last two decades, heterozygous loss-of-function PAX8 mutations have been reported in patients with a wide degree of thyroid gland dysfunction and growth despite the presence of identical mutations.ObjectivesTo search for PAX8 mutations in a cohort of patients with congenital hypothyroidism (CH) and various types of thyroid gland defects.DesignA cross-sectional study was conducted in a cohort of patients.SettingThe French neonatal screening program was used for recruiting patients.PatientsA total of 118 patients with CH, including 45 with familial and 73 with sporadic diseases, were included in this study. The thyroid gland was normal in 23 patients had hypoplasia, 25 had hemithyroid agenesis, 21 had athyreosis, and 21 had ectopy.ResultsWe found four different PAX8 mutations (p.R31C, p.R31H, p.R108X, and p.I47T) in ten patients (six patients with CH and four family members), two with sporadic and eight with familial diseases. Imaging studies performed in the index cases showed ectopic thyroid gland (n=2), hypoplasia (n=2), eutopic lobar asymmetry (n=1), and eutopic gland compatible with dyshormonogenesis (n=1). The previously reported p.R31C and the novel p.I47T PAX8 mutations are devoid of activity.ConclusionFour different PAX8 mutations were detected in six index patients with CH (ten total subjects). The p.R31C, p.R31H, and p.R108X mutations have been reported. The novel p.I47T PAX8 mutation presented loss of function leading to CH. Thyroid ectopy was observed in two cases of PAX8 (p.R31H) mutation, a finding that has not been reported previously. We observed a high inter-individual and intra-familial variability of the phenotype in PAX8 mutations, underlining that population genetic studies for CH should include patients with various clinical presentations.

scholarly journals Congenital Hypothyroidism Caused by a PAX8 Gene Mutation Manifested as Sodium/Iodide Symporter Gene Defect

2010 ◽  
Vol 2010 ◽  
pp. 1-3 ◽  
Author(s):  
Wakako Jo ◽  
Katsura Ishizu ◽  
Kenji Fujieda ◽  
Toshihiro Tajima
Keyword(s):  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Sodium Iodide ◽  
Present Report ◽  
Sodium Iodide Symporter ◽  
Loss Of Function ◽  
Laboratory Findings ◽  
Iodide Transport ◽  
Transport Defect ◽  
Pax8 Gene

Loss-of-function mutations of the PAX8 gene are considered to mainly cause congenital hypothyroidism (CH) due to thyroid hypoplasia. However, some patients with PAX8 mutation have demonstrated a normal-sized thyroid gland. Here we report a CH patient caused by a PAX8 mutation, which manifested as iodide transport defect (ITD). Hypothyroidism was detected by neonatal screening and L-thyroxine replacement was started immediately. Although I scintigraphy at 5 years of age showed that the thyroid gland was in the normal position and of small size, his iodide trapping was low. The ratio of the saliva/plasma radioactive iodide was low. He did not have goiter; however laboratory findings suggested that he had partial ITD. Gene analyses showed that the sodium/iodide symporter (NIS) gene was normal; instead, a mutation in the PAX8 gene causing R31H substitution was identified. The present report demonstrates that individuals with defective PAX8 can have partial ITD, and thus genetic analysis is useful for differential diagnosis.

scholarly journals Characterization of a Novel Loss of Function Mutation of PAX8 in a Familial Case of Congenital Hypothyroidism with In-Place, Normal-Sized Thyroid

2004 ◽  
Vol 89 (9) ◽  
pp. 4285-4291 ◽  
Author(s):  
Laurent Meeus ◽  
Brigitte Gilbert ◽  
Catherine Rydlewski ◽  
Jasmine Parma ◽  
Anne Lienhardt Roussie ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Congenital Hypothyroidism ◽  
Novel Mutation ◽  
Gene Promoter ◽  
Loss Of Function ◽  
Thyroid Dysgenesis ◽  
Cis Element ◽  
Ability To Act ◽  
Pax8 Gene ◽  
Functional Analyses

Thyroid dysgenesis is the most common cause of congenital hypothyroidism, a relatively frequent disease affecting 1 in 3000–4000 newborns. Whereas most cases are sporadic, mutations in transcription factors implicated in thyroid development have been shown to cause a minority of cases transmitted as monogenic Mendelian diseases. PAX8 is one of these transcription factors, and so far, five mutations have been identified in its paired domain in patients with thyroid dysgenesis. We have identified a novel mutation of PAX8, in the heterozygous state, in a father and his two children both presenting with congenital hypothyroidism associated with an in-place thyroid of normal size at birth. In addition, one of the affected siblings displayed unilateral kidney agenesis. The mutation substitutes a highly conserved serine in position 54 of the DNA-binding domain of the protein (S54G mutation) by a glycine. Functional analyses of the mutant protein (PAX8-S54G) demonstrated that it is unable to bind a specific cis-element of the thyroperoxidase gene promoter in EMSAs and that it has almost completely lost the ability to act in synergy with Titf1 to transactivate transcription from the thyroglobulin promoter/enhancer. These results indicate that loss of function mutations of the PAX8 gene may cause congenital hypothyroidism in the absence of thyroid hypoplasia.

Compound heterozygous mutations (p.T561M and c.2422delT) in the TPO gene associated with congenital hypothyroidism

2016 ◽  
Vol 29 (5) ◽  
Author(s):  
Shao-Gang Ma ◽  
Xiao Zheng ◽  
Ya-Li Qiu ◽  
Man-Li Guo ◽  
Xiao-Juan Shao
Keyword(s):  
Molecular Analysis ◽  
Congenital Hypothyroidism ◽  
Genetic Basis ◽  
Compound Heterozygous ◽  
Dual Oxidase ◽  
Compound Heterozygous Mutations ◽  
Inactivating Mutations

AbstractThe objective of the study was to determine the genetic basis of goitrous congenital hypothyroidism (GCH) in Chinese siblings.The proband and her younger brother with GCH were enrolled for molecular analysis of the dual oxidase 2 (Analysis of theThe inactivating mutations (c.2422delT and p.T561M) in the

Genetic Variability of the Paired Box Transcription Factor; PAX8 Gene: Guidance Towards Treatment Strategies in a Cohort of Congenital Hypothyroidism

2021 ◽  
Author(s):  
Sohier S. Abou El-Ella ◽  
Essam Shawky A.E.H. Khattab ◽  
Rehab K. Beddah ◽  
Naglaa Fathy Barseem
Keyword(s):  
Genetic Variability ◽  
Congenital Hypothyroidism ◽  
Novel Mutation ◽  
Treatment Strategies ◽  
Group I ◽  
Egyptian Patients ◽  
Pax8 Gene ◽  
Healthy Control ◽  
And Function ◽  
Thyroid Development

AbstractThe contribution of PAX8 genetic variants to congenital hypothyroidism (CH) is not well understood. We aimed to study the genetic variability of exons 3 and 5 of PAX8 gene among a cohort of children with congenital hypothyroidism in correspondence to their clinical aspect. Blood samples were collected from 117 children (63 girls and 54 boys) with CH and enrolled as cases (Group I). All cases underwent biochemical confirmation with low FT4 and high TSH levels and thyroid gland imaging, along with equal number of matched apparently healthy individuals who served as controls (Group II). Genomic materials for exons 3 and 5 of PAX8 gene were extracted, amplified by PCR, detected by electrophoresis, purified, and sequenced by the Sanger technique through the application of ABI 3730x1 DNA Sequencer. Out of 117 cases, eight different effective PAX8 mutations were detected in exon 3 (G23D, V35I, I34T, Q40P, p.R31C, p.R31H, p.R31A, and p.I47T) in 14 patients with their sonographic findings ranged from normal, hypoplastic to thyroid agenesis. Besides the reported mutations, one novel mutation; R31A was detected in 1 euotopic case. Exon 5 analysis revealed no detected mutations elsewhere. In contrast, all healthy control children showed no mutation and normal sonographic findings. Mutations in exon 3 of PAX8 gene, implies its important role in thyroid development and function, as a first estimate of PA8 mutation rate in Egyptian patients with CH having normal and dysgenetic gland. Using ultrasound is mandatory for diagnosis and guiding the treatment of children with CH.

scholarly journals A molecular analysis and long-term follow-up of two siblings with severe congenital hypothyroidism carrying the IVS30+1G>T intronic thyroglobulin mutation

2008 ◽  
Vol 52 (8) ◽  
pp. 1337-1344 ◽  
Author(s):  
Ileana G. S. Rubio ◽  
Ana Luiza Galrao ◽  
Viviane Pardo ◽  
Meyer Knobel ◽  
Roberta F. Possato ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Congenital Hypothyroidism ◽  
Thyroid Tissue ◽  
Endoplasmatic Reticulum ◽  
Iodine Nutrition ◽  
Genes Expression ◽  
Long Term Follow Up ◽  
Tissue Specimens

OBJECTIVE: To extend the molecular analysis of the IVS30+1G>T intronic thyroglobulin (TG) mutation, and to report the eleven year follow-up of the affected patients. METHOSD: Two siblings with severe congenital hypothyroidism with fetal and neonatal goiter, harboring the IVS30+1G>T mutation were included. Nodular and non-nodular thyroid tissue specimens were collected. Specific thyroid genes expression was evaluated by real-timePCR and by immunohistochemistry. RESULTS: In non-nodular tissue specific thyroid genes mRNA were reduced when compared to normal thyroid sample. In the nodule, TPO and NIS expression was very low. Microscopic examinations showed very large follicular-lumina and swollen vesicles of endoplasmatic-reticulum. Strong cytoplasmatic and low follicular-lumen TG immunostaining were detected. Intracellular NIS, membrane TPO and TSHR immunostaining had higher positivity in non-nodular sample. Both patients had a long-term adequate developmental outcome, besides one patient have been lately-treated. CONCLUSIONS: IVS30+1G>T mutation not only lead to very enlarge endoplasmatic-reticulum, but also to alterations of specific thyroid genes expression. The clinical evolution of patients harboring these mutations strengthen the concept of the influence of environment, like iodine nutrition, to determine the final phenotypic appearance.

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