Congenital hypothyroidism
Gene: PAX8Comment 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.
Rarely associated urorgenital tract malformations. Classically thyroid hypoplasia although agenesis and ectopic-gland-in-situ also occurCreated: 11 Feb 2017, midnight
Strong evidence for cause of congenital hypothyroidismCreated: 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
22 February 2017: Promoted to Version 1. Reviews were assessed, and panel was revised according to expert review and additional curation. After discussion with the reviewer and in-house clinicians, it was agreed to include the genes for 'combined pituitary hormone deficiency' (CPHD) on the panel, since patients can present with central hypothyroidism (CH). In these cases, CH does not occur in isolation, but is one of the evolving pituitary hormone deficiencies.
This gene has been classified as Green List (High Evidence).
Publications for PAX8 were set to PMID:23647375; PMID:9590296
Mode of inheritance for PAX8 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for PAX8 were set to 23647375; 9590296
Phenotypes for PAX8 were set to Congenital hypothyroidism; Hypothyroidism, Congenital, Nongoitrous, 2, 218700; Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, 218700; urogenital tract malformations; thyroid hypoplasia; thyroid dysgenesis; eutopic gland-in-situ
PAX8 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Radboud University Medical Center, Nijmegen
Phenotypes for gene PAX8 were set to Congenital hypothyroidism; Hypothyroidism, Congenital, Nongoitrous, 2, 218700
PAX8 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: UKGTN
PAX8 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Emory Genetics Laboratory
PAX8 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Illumina TruGenome Clinical Sequencing Services
PAX8 was created by oniblock