Congenital Hypothyroidism: FOXE1 Gene Deletion/Duplication
Test Code: 8953
Turnaround time: 3 weeks
Congenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. In 80-85% of cases, the thyroid gland is absent (agenesis), ectopically located, and/or severely reduced in size (hypoplasia) . In the remaining cases, a normal-sized or enlarged thyroid gland is present, but production of thyroid hormones is decreased or absent. If treatment begins in the first month after birth, infants usually develop normally. When thyroid hormone therapy is not initiated within the first two months of life, however, congenital hypothyroidism can cause severe neurologic, mental, and motor damage (cretinism). In the United States and many other countries, all newborns are tested for congenital hypothyroidism.
Mutations in the FOXE1 (9q22) gene have been associated with Bamforth Lazarus syndrome (BLS). In addition to congenital hypothyroidism, other characteristics of BLS can include bilateral choanal atresia, cleft palate, bifid epiglottis, and spiky or curly hair. Hypothyroidism can be due to athyreosis or a nonfunctional eutopic thyroid. Sequencing of the FOXE1 gene is recommended after a biochemical diagnosis of congenital hypothyroidism that presents with the characteristics listed above. It can be used to confirm the presence of mutations in a proband, identify carriers among the proband’s relatives, and provide prenatal diagnosis in families with known mutations.
This test is indicated for:
- Confirmation of a clinical diagnosis of congenital hypothyroidism presenting with choanal atresia, cleft palate, and spiky hair in individuals who have tested negative for sequence analysis
DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.
Please note that a “backbone” of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off- target copy number variants causative of disease may be identified that may or may not be related to the patient’s phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient’s clinical and/or biochemical phenotype.
Submit only 1 of the following specimen types
* Preferred specimen type: Whole Blood
Type: Whole Blood
In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
Submit copies of diagnostic biochemical test results with the sample, if appropriate.
Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed by another third party provider, please submit a copy of the sequencing report with the test requisition.
- Sequence analysis of the FOXE1 gene is available and is required before deletion/duplication analysis.