Congenital hypothyroidism

Gene: PAX8

Comment when marking as ready: 1 Green review plus confirmed DD-G2P gene for MIM:218700. Plus >3 cases of PAX8 mutations causing Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, 218700.

Created: 13 Feb 2017, 10:29 a.m.

Marked as 'incomplete penetrance' based on PMID:11502839 (Congdon et al., 2001) who identify heterozygosity for a 119A-C transversion (Q40P) in a girl with congenital hypothyroidism and thyroid gland hypoplasia. The mother, who had a thyroid gland of normal size and mild, adult-onset autoimmune hypothyroidism, was also heterozygous for the mutation. Macchia et al., 1998 (PMID:9590296) also note clinical variability in a proband's mother and sister who were heterozygous for the same mutation as the proband (L62R) but displayed clinical variability: the mother had been diagnosed with hypothyroidism at age 10 and had a hypoplastic thyroid gland, whereas the sister had a thyroid of a size at the lower limit of normal, with normal thyroid hormone levels but high TSH values.

Created: 13 Feb 2017, 10:27 a.m.

Comment on mode of inheritance: Monoallelic mode of inheritance confirmed by OMIM and G2P.

Created: 13 Feb 2017, 10:20 a.m.

Green List (high evidence)

Rarely associated urorgenital tract malformations. Classically thyroid hypoplasia although agenesis and ectopic-gland-in-situ also occur

Created: 11 Feb 2017, midnight

Strong evidence for cause of congenital hypothyroidism

Created: 10 Feb 2017, 11:54 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
urogenital tract malformations; thyroid hypoplasia; thyroid dysgenesis; eutopic gland-in-situ

Publications

• PMID: 23647375
• PMID: 9590296