Congenital hypothyroidism

Gene: PAX8

Green List (high evidence)

PAX8 (paired box 8)
EnsemblGeneIds (GRCh38): ENSG00000125618
EnsemblGeneIds (GRCh37): ENSG00000125618
OMIM: 167415, Gene2Phenotype
PAX8 is in 4 panels

2 reviews

Rebecca Foulger (Genomics England curator)

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.

Nadia Schoenmakers (University of Cambridge)

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • 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
OMIM
167415
Clinvar variants
Variants in PAX8
Penetrance
Incomplete
Publications
Panels with this gene

History Filter Activity

22 Feb 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

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.

13 Feb 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

13 Feb 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for PAX8 were set to PMID:23647375; PMID:9590296

13 Feb 2017, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for PAX8 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

13 Feb 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for PAX8 were set to 23647375; 9590296

13 Feb 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

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

23 Jan 2017, Gel status: 4

Added New Source

Rebecca Foulger (Genomics England curator)

PAX8 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Radboud University Medical Center, Nijmegen

23 Jan 2017, Gel status: 3

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene PAX8 were set to Congenital hypothyroidism; Hypothyroidism, Congenital, Nongoitrous, 2, 218700

13 Oct 2016, Gel status: 3

Added New Source

Olivia Niblock (Genomics England Curator)

PAX8 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: UKGTN

13 Oct 2016, Gel status: 2

Added New Source

Olivia Niblock (Genomics England Curator)

PAX8 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Emory Genetics Laboratory

13 Oct 2016, Gel status: 1

Added New Source

Olivia Niblock (Genomics England Curator)

PAX8 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Illumina TruGenome Clinical Sequencing Services

13 Oct 2016, Gel status: 0

Created

Olivia Niblock (Genomics England Curator)

PAX8 was created by oniblock