Congenital hypothyroidism

Gene: IGSF1

Green List (high evidence)

IGSF1 (immunoglobulin superfamily member 1)
EnsemblGeneIds (GRCh38): ENSG00000147255
EnsemblGeneIds (GRCh37): ENSG00000147255
OMIM: 300137, Gene2Phenotype
IGSF1 is in 5 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Rated green, >3 unrelated cases from diverse populations and Mode of inheritance supported by literature and reviewer.
Created: 14 Feb 2017, 10:25 a.m.
Comment on list classification: Updated rating from Grey to Green. One green review (from gene submitter), Confirmed DD-G2P gene for hypothyroidism (MIM:300888). Plus >3 cases of IGSF1 mutations causing hypothyroidism in multiple populations (including Dutch, Japanese and British).
Created: 14 Feb 2017, 10:23 a.m.
Comment on mode of inheritance: OMIM records an XLR inheritance but PMID:24108313 states that a minority of female heterozygous carriers exhibits central hypothyroisim (6 of 18 cases, 33%).
Created: 14 Feb 2017, 10:22 a.m.

Nadia Schoenmakers (University of Cambridge)

Green List (high evidence)

Affected males all have central hypothyroidism, > 60% have low basal prolactin, ~16% have GH deficiency in childhood and most have macroorchidism in adulthood. 25% females have central hypothyroidism and smaller numbers have hypoprolactinaemia.
Created: 11 Feb 2017, 12:52 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
central hypothyroidism; hypoprolactinaemia; GH deficiency; macroorchidism

Publications

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
Phenotypes
  • central hypothyroidism
  • hypoprolactinaemia
  • GH deficiency
  • macroorchidism
  • Hypothyroidism, central, and testicular enlargement, 300888
OMIM
300137
Clinvar variants
Variants in IGSF1
Penetrance
Complete
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.

14 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).

14 Feb 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for IGSF1 were set to 23143598; 26840047; 27762734; 24108313 (reports that a subset of female carriers show central hypothyroidism).

14 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).

14 Feb 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for IGSF1 was changed to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

14 Feb 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for IGSF1 were set to 23143598; 26840047; 27762734

14 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene IGSF1 were set to central hypothyroidism; hypoprolactinaemia; GH deficiency; macroorchidism; Hypothyroidism, central, and testicular enlargement, 300888

11 Feb 2017, Gel status: 0

Created

Nadia Schoenmakers (University of Cambridge)

IGSF1 was created by [email protected]

11 Feb 2017, Gel status: 0

Added New Source

Nadia Schoenmakers (University of Cambridge)

IGSF1 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature