Hypothyroidism, Congenital, Nongoitrous, 5

A number sign (#) is used with this entry because congenital nongoitrous hypothyroidism-5 (CHNG5) is caused by heterozygous mutation in the NKX2-5 gene (600584) on chromosome 5q35.

For a general phenotypic description and a discussion of genetic heterogeneity of congenital nongoitrous hypothyroidism, see 275200.

Molecular Genetics

Dentice et al. (2006) screened for mutations in the coding region of the NKX2-5 gene (600584) in 241 patients with congenital nongoitrous hypothyroidism, including 53 with athyreosis, 99 with thyroid ectopy, and 15 with hypoplasia, and identified 3 different heterozygous missense mutations in 4 of the patients: 2 of the mutations were novel (600584.0015-600584.0016) and the other had previously been identified in patients with congenital heart disease (600584.0004). Functional characterization of the 3 mutations demonstrated reduced DNA binding and/or transactivation properties, with a dominant-negative effect on wildtype NKX2-5.