Background: Homozygous loss-of-function mutations in the FOXE1 gene have been reported in several patients with partial or complete Bamforth-Lazarus syndrome: congenital hypothyroidism (CH) with thyroid dysgenesis (usually athyreosis), cleft palate, spiky hair, with or without choanal atresia, and bifid epiglottis. Here, our objective was to evaluate potential functional consequences of a FOXE1 mutation in a patient with a similar clinical phenotype.

Methods: FOXE1 was sequenced in eight patients with thyroid dysgenesis and cleft palate. Transient transfection was performed in HEK293 cells using the thyroglobulin (TG) and thyroid peroxidase (TPO) promoters in luciferase reporter plasmids to assess the functional impact of the FOXE1 mutations. Primary human thyrocytes transfected with wild type and mutant FOXE1 served to assess the impact of the mutation on endogenous TG and TPO expression.

Results: We identified and characterized the function of a new homozygous FOXE1 missense mutation (p.R73S) in a boy with a typical phenotype (athyreosis, cleft palate, and partial choanal atresia). This new mutation located within the forkhead domain was inherited from the heterozygous healthy consanguineous parents. In vitro functional studies in HEK293 cells showed that this mutant gene enhanced the activity of the TG and TPO gene promoters (1.5-fold and 1.7-fold respectively vs. wild type FOXE1; p<0.05), unlike the five mutations previously reported in Bamforth-Lazarus syndrome. The gain-of-function effect of the FOXE1-p.R73S mutant gene was confirmed by an increase in endogenous TG production in primary human thyrocytes.

Conclusion: We identified a new homozygous FOXE1 mutation responsible for enhanced expression of the TG and TPO genes in a boy whose phenotype is similar to that reported previously in patients with loss-of-function FOXE1 mutations. This finding further delineates the role for FOXE1 in both thyroid and palate development, and shows that enhanced gene activity should be considered among the mechanisms underlying Bamforth-Lazarus syndrome.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993030PMC
http://dx.doi.org/10.1089/thy.2013.0417DOI Listing

Publication Analysis

Top Keywords

cleft palate
12
foxe1 mutation
8
bamforth-lazarus syndrome
8
thyroid dysgenesis
8
athyreosis cleft
8
choanal atresia
8
hek293 cells
8
wild type
8
foxe1
7
mutation
5

Similar Publications

What are the Pterygomaxillary Fracture Patterns in Cleft Orthognathic Surgery?

J Oral Maxillofac Surg

December 2024

Professor, Faculty of Dentistry of Bauru, Department of Surgery, Stomatology, Pathology and Radiology, University of São Paulo, Bauru, São Paulo, Brazil; Professor, Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo (HRAC/USP), Bauru, São Paulo, Brazil.

Background: Patients with cleft lip and palate (CLP) often exhibit unique anatomical variations in the pterygoid plates, which can influence fracture patterns at the pterygomaxillary junction (PMJ) during Le Fort I osteotomy. These differences may increase the risk of unfavorable fractures, complicating surgery and recovery.

Purpose: The study purpose was to measure the association between the osteotomy level with the PMJ fracture patterns in CLP patients undergoing Le Fort I osteotomy.

View Article and Find Full Text PDF

Cleft palate is the most prevalent congenital condition. Cleft palate is brought on by an exogenous chemical called all-trans retinoic acid (atRA). In order to indirectly control gene expression, long chain non-coding RNAs (lncRNAs) act as competitive endogenous RNA (ceRNA) sponges.

View Article and Find Full Text PDF

Background: Ring 18 chromosome is a rare chromosomal aberration associated with a wide range of symptoms affecting all organ systems. One possible symptom associated with this condition is an orofacial cleft. However, to date, there are very few reported cases where the cleft has been surgically treated.

View Article and Find Full Text PDF

Comparison of two different secondary rhinoplasties in patients with complete unilateral cleft lip and palate.

BMC Surg

December 2024

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cleft Lip and Palate, West China School of Stomatology, Sichuan University, Chengdu, China.

Background: The purpose of this study was to analysis the nostril symmetry and nasal stability following secondary rhinoplasty performed with either nasal septal cartilage implantation (G1) or simple alar cartilage suspension and internal fixation (G2) in patients with unilateral secondary cleft nasal deformity.

Methods: Nostril and alar symmetry were analyzed retrospectively in 13 consecutive patients in G1 and 17 in G2. Assessment of three indexes was first performed using photogrammetric measurements of photographs at pre-operation(T1), 7 days after repair (T2), and at least 6 months after repair (T3).

View Article and Find Full Text PDF

Transcriptional factor ISL1 regulates palate development by tuning the SHH cascade.

FEBS J

December 2024

Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, China.

Cleft palate is one of the most common birth defects in humans, and palate morphogenesis depends on epithelial-mesenchymal interaction. In this study, we report that ablation of Isl1 in the epithelium leads to complete cleft palate. A significant reduction in mesenchymal cell proliferation was detected in the Isl1 mutant palates, but there was no significant difference in apoptosis between wild-type and mutant embryos.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!