Congenital hypothyroidism
Gene: IGSF1Comment 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.
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
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 IGSF1 were set to 23143598; 26840047; 27762734; 24108313 (reports that a subset of female carriers show central hypothyroidism).
This gene has been classified as Green List (High Evidence).
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)
Publications for IGSF1 were set to 23143598; 26840047; 27762734
Phenotypes for gene IGSF1 were set to central hypothyroidism; hypoprolactinaemia; GH deficiency; macroorchidism; Hypothyroidism, central, and testicular enlargement, 300888
IGSF1 was created by [email protected]
IGSF1 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature