Studies have shown that 2% of congenital hypothyroidism patients with thyroid dysgenesis have a positive familial history . A segregation analysis led to the conclusion that thyroid developmental abnormalities are compatible with an autosomal dominant mode of inheritance with a low penetrance . Mutations in many genes are known to cause congenital hypothyroidism. Multiple affected individuals have been shown to be heterozygous for mutations in the Paired Box Gene 8 (PAX8 2q12-q14), including individuals with positive family histories [4-8].
1. Macchia et al. PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis. Nature Genet. 1998, 19:83-86.
2. Castanet et al. Familial forms of thyroid dysgenesis among infants with congenital hypothyroidism. (Letter) New Eng. J. Med. 2000, 343:441-442. 3. Leger et al. Thyroid developmental anomalies in first degree relatives of children with congenital hypothyroidism. J. Clin. Endocr. Metab. 2002, 87:575-580.
4. Macchia et al. PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis. Nature Genet. 1998, 19:83-86.
5. Vilain et al. Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8. J. Clin. Endocr. Metab. 2001, 86:234-238.
6. Congdon et al. A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: evidence for phenotypic variability in mother and child. J. Clin. Endocr. Metab. 2001, 86: 3962-3967.
7. Meeus et al. Characterization of a novel loss of function mutation of PAX8 in a familial case of congenital hypothyroidism with in-place, normal-sized thyroid. J. Clin. Endocr. Metab. 2004, 89: 4285-4291.
8. Grasberger et al. Thyroid transcription factor 1 rescues PAX8/p300 synergism impaired by a natural PAX8 paired domain mutation with dominant negative activity. Molec. Endocr. 2005, 19: 1779-1791.
- Confirmation of a clinical/biochemical diagnosis of congenital hypothyroidism.
Analytical Sensitivity: ~99%. Results of molecular analysis should be interpreted in the context of the patient's biochemical phenotype.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>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.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) 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.
- Known Mutation Analysis (KM) is available to family members if mutations are identified by sequencing.
- Prenatal Custom Diagnostics is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.