Non-syndromic hypotrichosis
Gene: HRComment on mode of inheritance: Updated MOI from 'monoallelic' to 'both mono- and biallelic'. Heterozygous variants in the 5'UTR of HR have been shown to cause Marie Unna hereditary hypotrichosis while homozygous variants have been associated with Alopecia universalis (MIM# 203655) and Atrichia with papular lesions (MIM# 209500), therefore both inheritance patterns are relevant to this panel.Created: 22 Feb 2022, 12:08 p.m. | Last Modified: 22 Feb 2022, 12:08 p.m.
Panel Version: 1.10
Comment on list classification: Updated rating from Red to Green after clinical discussion: 1 Green review, multiple 5'UTR HR variants causing Hypotrichosis (146550). Plus >3 cases of HR variants causing Atrichia with papular lesions, which includes 'Hypotrichosis' as a phenotype.Created: 2 Feb 2017, 4 p.m.
Added the tags 'non-coding known pathogenic', 'promoter' and 'curated variant list' based on the 4 reported variants in OMIM, all of which are reported to be in the 5'UTR of HR (in an ORF designated U2HR which encodes a (predicted?) peptide which modulates the translation of HR mRNA), with pathogenic clinical significance (rs267606869, rs267606868, rs267606867, rs387906382). See PMID:26269244, 24261346 etc for discussion of the U2HR ORF.Created: 2 Feb 2017, 3:56 p.m.
Comment on mode of pathogenicity: Hypotrichosis 4 (OMIM:146550, also called Marie Unna hereditary hypotrichosis) is caused by mutations in an ORF (designated U2HR) in the 5'UTR of the HR gene. The ORF appears to encode a short peptide which controls the translation of HR mRNA.Created: 24 Jan 2017, 4:24 p.m.
Comment on phenotypes: Mutations in the HR gene are also causative of Alopecia universalis (OMIM:203655) and Atrichia with papular lesions (OMIM:209500), both with biallelic inheritance. For Atrichia with papular lesions (OMIM:209500), 'Hypotrichosis' iis recorded in the OMIM Clinical synopsis.Created: 24 Jan 2017, 4:03 p.m.
Comment on mode of inheritance: Mode of inheritance confirmed by OMIM.Created: 23 Jan 2017, 4:38 p.m.
Well establishedCreated: 20 Jan 2017, 5:01 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Alopecia universalis; Atrichia with papular lesions; Hypotrichosis 4
Phenotypes for gene: HR were changed from Hypotrichosis 4, 146550; HYPT4; Marie Unna hereditary hypotrichosis 1 (MUHH1); Marie Unna hereditary hypotrichosis (MUHH) to Marie Unna hereditary hypotrichosis (MUHH); Alopecia universalis, OMIM:203655
Mode of inheritance for gene: HR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
20 February 2017: Panel review was assessed, and panel was revised according to expert review and additional curation. Queried with the expert reviewer whether the 'Non-syndromic hypotrichosis' and 'cicatricial alopecia' panels should be combined based on overlapping phenotypes. Celia Moss commented that dermatologists consider cicatricial (scarring) alopecia distinct from simple hypotrichosis (in which there is no scarring); therefore have kept the panels separate.
This gene has been classified as Green List (High Evidence).
Mode of pathogenicity for HR was changed to Other - please provide details in the comments
Phenotypes for HR were set to Hypotrichosis 4, 146550; HYPT4; Marie Unna hereditary hypotrichosis 1 (MUHH1); Marie Unna hereditary hypotrichosis (MUHH)
Mode of inheritance for HR was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene HR were set to Hypotrichosis 4, 146550; HYPT4; Marie Unna hereditary hypotrichosis 1 (MUHH1);Marie Unna hereditary hypotrichosis (MUHH)
HR was added to Non-syndromic hypotrichosispanel. Source: Radboud University Medical Center, Nijmegen
HR was created by rfoulger
HR was added to Non-syndromic hypotrichosispanel. Sources: Other