Congenital hypothyroidism
Gene: PROP1Comment on list classification: Updated rating from Grey to Green: 1 Green review (from gene submitter). Plus plenty (well over 3) cases of PROP1 mutations causing combined pituitary hormone deficiency, which can present with CH. At least 3 cases mention hypothyroidism specifically (PMID:16984240, 23652424, 15472175).Created: 21 Feb 2017, 11:25 a.m.
PMID:16984240 (Lemos et al., 2006) perfomed a multicentre study involving 46 cases of combined pituitary hormone deficiency (CPHD); 17 cases belonging to 7 unrelated families, and 29 sporadic cases. PROP1 mutations were identified in all 17 familial cases and in 2 of the sporadic cases. All 19 patients with germline mutations had presented with growth retardation and central hypothyroidism during childhood.Created: 21 Feb 2017, 11:22 a.m.
PMID:23652424 (Wassner et al., 2013) present two young siblings (age 6 months and 2 years) presenting with central hypothyroidism (CH). A homozygous frameshift mutation in PROP1 (296DelGA) was identified in both probands.Created: 21 Feb 2017, 11:14 a.m.
Lee et al., 2004 (PMID:15472175) report 3 adult siblings with short stature, hypothyroidism, and lack of pubertal maturation who were homozygous for 301–302delAG PROP-1 mutation. The mother and the father are heterozygous for the mutation.Created: 21 Feb 2017, 11:10 a.m.
PROP1 is a late pituitary transcription factor. Mutations in early or late pituitary transcription factors may cause central hypothyroidism (CH), a particular hypothyroid condition due to an insufficient stimulation by TSH of an otherwise normal thyroid gland. In these cases, CH does not occur in isolation, but is one of the evolving pituitary hormone deficiencies [PMID:26416826].Created: 21 Feb 2017, 10:35 a.m.
Comment on mode of inheritance: Mode of inheritance confirmed by OMIM and G2P.Created: 20 Feb 2017, 12:07 p.m.
Confirmed DD-G2P gene for combined pituitary hormone deficiency (MIM:262600).Created: 20 Feb 2017, 12:07 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
GH, TSH, LH, FSH, PRL deficiency with variable age of onset, evolving ACTH deficiency. Commonest cause of combined pituitary hormone deficit without extra pituitary manifestations. Hypoplastic or normal anterior pituitary although there have been reports of an enlarged anterior pituitary at initial scanning in childhood with spontaneous involution over time.
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.
Phenotypes for PROP1 were set to GH, TSH, LH, FSH, PRL deficiency with variable age of onset, evolving ACTH deficiency; Commonest cause of combined pituitary hormone deficit without extra pituitary manifestations; Hypoplastic or normal anterior pituitary although there have been reports of an enlarged anterior pituitary at initial scanning in childhood with spontaneous involution over time; Pituitary hormone deficiency, combined, 2, 262600
This gene has been classified as Green List (High Evidence).
Publications for PROP1 were set to 9768691; 15126542; 15472175; 26416826 (2015 review); 23652424; 16984240
Mode of inheritance for PROP1 was changed to BIALLELIC, autosomal or pseudoautosomal
Publications for PROP1 were set to 9768691; 15126542
Phenotypes for PROP1 were set to GH, TSH, LH, FSH, PRL deficiency with variable age of onset, evolving ACTH deficiency. Commonest cause of combined pituitary hormone deficit without extra pituitary manifestations. Hypoplastic or normal anterior pituitary although there have been reports of an enlarged anterior pituitary at initial scanning in childhood with spontaneous involution over time; Pituitary hormone deficiency, combined, 2, 262600
PROP1 was created by [email protected]
PROP1 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature