Ichthyosis and erythrokeratoderma
Gene: SREBF1
Comment on classification of this gene: The rating for this gene should be added as GREEN, as this gene has been implicated in ichthyosis and erythrokeratoderma, as identified from monoallelic variants from at least 18 unrelated individuals/ families from multiple ethnicities, and supported by results from in vitro functional studies.
As reviewed by Zornitza Stark, heterozygous variants in 11 unrelated, ethnically diverse individuals has resulted in IFAP syndrome (MIM# 619016), which is characterised generally by moderate or severe hypotrichosis or atrichia (hair), ichthyosis follicularis (skin), and photophobia, Meibomian gland dysfunction, keratitis and/or cataract (eye) (PMID:32497488). Similarly, autosomal-dominant IFAP syndrome was also observed in another report of a Japanese woman and her daughter displaying heterozygous variant c.1669C>T (p.Arg557Cys) in SREBF1 gene (PMID:33253727).
Seven patients from four families displaying heterozygous variants of SREBF1 gene (c.1669C>T (p.Arg557Cys) and c.1670G>A (p.Arg557His)) were reported with HMD (MIM# 158310), which is characterised by chronic keratitis, non-scarring alopecia, mucosal erythema, keratosis pilaris, perineal erythematous intertrigo, psoriatic-like perineal plaques, and involvement of the conjunctival mucosa (PMID:31790666). There are also another two reports of patients with c.1669C>T (p.Arg557Cys) variant displaying autosomal-dominant HMD (PMID:32902915, PMID:33742461). The clinical indications of IFAP and HMD suggests that these two diseases share a common clinical spectrum.
The association of both IFAP and HMD to SREBF1 has been documented in OMIM. In addition, results from in vitro investigation of SREBP1 variants confirms the essential role of SREBF1 in epidermal differentiation, skin barrier formation, hair growth, and eye function (PMID:32497488).Created: 9 Dec 2022, 6:12 p.m. | Last Modified: 9 Dec 2022, 6:12 p.m.
Panel Version: 2.7
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Ichthyosis, follicular, with atrichia and photophobia syndrome 2, MIM# 619016, MONDO:0100221; Hereditary mucoepithelial dysplasia, MIM# 158310, MONDO:0008017
Publications
11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. 3 different msisense variants identified affecting the same region (residues 527, 528, and 530). Functional studies support impaired function (impaired nuclear translocation of the transcriptionally active form of SREBP1 resulting in lower expression of the SREBP1 variants). Increased keratinocyte apoptosis was observed in patient scalp samples.
Sources: LiteratureCreated: 6 Jul 2020, 7:45 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome
Publications
Tag Q4_22_promote_green tag was added to gene: SREBF1.
Phenotypes for gene: SREBF1 were changed from IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome to Ichthyosis, follicular, with atrichia and photophobia syndrome 2, MIM# 619016, MONDO:0100221; Hereditary mucoepithelial dysplasia, MIM# 158310, MONDO:0008017
Publications for gene: SREBF1 were set to 32497488
Gene: srebf1 has been classified as Amber List (Moderate Evidence).
gene: SREBF1 was added gene: SREBF1 was added to Ichthyosis and erythrokeratoderma. Sources: Literature Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SREBF1 were set to 32497488 Phenotypes for gene: SREBF1 were set to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome Review for gene: SREBF1 was set to GREEN