Non-syndromic hypotrichosis

Gene: HR

Green List (high evidence)

Comment on phenotypes: Monoallleic HRURF variants are associated with Hypotrichosis 4, OMIM:146550

Created: 9 Aug 2024, 2:35 p.m. | Last Modified: 9 Aug 2024, 2:35 p.m.

Panel Version: 1.14

Biallelic variants in the gene HR (OMIM: 602302) are associated with Alopecia universalis (OMIM:203655) and Atrichia with papular lesions (OMIM:209500). Monoallleic variants in the gene HRURF (OMIM:619257) are associated with Hypotrichosis 4 (OMIM:146550). The five HRURF variants listed in OMIM, are variants which have been moved from HR.
It is not possible to add the gene HRURF to PanelApp at this time.

Created: 9 Aug 2024, 2:24 p.m. | Last Modified: 9 Aug 2024, 2:24 p.m.

Panel Version: 1.13

Comment 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.

Green List (high evidence)

Well established

Created: 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