Review 'epidermolytic ichthyosis' (MONDO:0007239)

[sabrinatoro]

'epidermolytic ichthyosis' (MONDO:0007239) = OMIM:113800

There is a new OMIMPS: 'epidermolytic hyperkeratosis' (MONDO:0957316)

According to the OMIMPS, 'epidermolytic ichthyosis' (MONDO:0007239) should be a child of 'epidermolytic hyperkeratosis' (MONDO:0957316). However the current record for MONDO:0957316 might include several concepts.

x-refs should be reviewed for (MONDO:0957316). There might be a term split/merge required

[kanems]

I agree this needs review... OMIM 113800 does not seem to be a correct match to this term, so it probably needs to split out to its own entry that is a child of the Orpha:312 entry and also a child of MONDO:0957316 But i am not sure if the Orpha:312 is actually a direct child of the OMIM PS? The synonyms from Orphanet suggest that the epidermolytic -hyperkeratosis and -ichthysosis concepts are interchangeable?

[sabrinatoro]

This is a complicated issue. I am adding my analysis in 3 different comments, including the to-do list. @kanems, @nicolevasilevsky, @twhetzel , when you have a moment, could you please take a look at my analysis and let me know if you agree/disagree? Thank you!

[sabrinatoro]

Comment 1: "epidermolytic hyperkeratosis 2"

The existing OMIM:620150 (currently referring to MONDO:0958184 'epidermolytic hyperkeratosis 2') was recently updated in OMIM (on 02/07/2024). 2 terms now represents 'epidermolytic hyperkeratosis 2'

• OMIM:620707 - Epidermolytic hyperkeratosis 2B, autosomal recessive (Gene affected = KRT10)
• OMIM:620150 - Epidermolytic hyperkeratosis 2A, autosomal dominant (Gene affected = KRT10)

I think we should keep MONDO:0958184 'epidermolytic hyperkeratosis 2 (Gene affected = KRT10) as a grouping term as it is used in other sources such as DOID:0081359 = epidermolytic hyperkeratosis 2 = gene affected KRT10.

TO DO:

• [ ] update definition for MONDO:0958184 to include “epidermolytic hyperkeratosis and 'has material basis in germline mutation in' some KRT10)
• [ ] remove x-ref OMIM:620707 from MONDO:0958184
• [ ] add x-ref DOID:0081359 to MONDO:0958184
• [ ] create 2 new terms corresponding to OMIM:620707 and OMIM:620150

[sabrinatoro]

Comment 2: "general classification"

General classification should follow orphanet. Parent term = Keratinopathic ichthyosis (ORDO:281103) = MONDO:0017266 Children: Term names in orphanet	Orphanet ID	OMIM mappings according to Orphanet	Mondo ID corresponding to Orphanet (and OMIM when only 1 omim mapping)	Status in Mondo
Annular epidermolytic ichthyosis	ORDO:281139	OMIM:607602OMIM:620148	MONDO:0011870	OK. The Mondo term has 2 children corresponding to the 2 omimRemove the parentage to 'autosomal dominant epidermolytic ichthyosis' (MONDO:0020702)
Autosomal dominant epidermolytic ichthyosis	ORDO:312	OMIM:113800OMIM:607602	MONDO:0007239	The orphanet mapping to omim is incorrect now that omim split OMIM:607602 (see comment 1)Add ORDO:312 to the Mondo recordSee reclassification in comment 3
Autosomal recessive epidermolytic ichthyosis	ORDO:512103		MONDO:0044742	OKSee reclassification in comment 3
Congenital reticular ichthyosiform erythroderma	ORDO:281190	OMIM:609165	MONDO:0012208	Make this term a child of the parent term: MONDO:0017266
Epidermolytic nevus	ORDO:497737		MONDO:0044656	OK
Ichthyosis hystrix of Curth-Macklin	ORDO:79503	OMIM:146590	MONDO:0007808	Make this term a child of the parent term: MONDO:0017266
Superficial epidermolytic ichthyosis	ORDO:455	OMIM:146800	MONDO:0007813	OK

[sabrinatoro]

Comment 3: "Epidermolytic hyperkeratosis"

finding 1: From PMID:28815464 Epidermolytic ichthyosis is the major variant of keratinopathic ichthyosis, an umbrella term for ichthyosis caused mostly by dominant-negative mutations in the keratin genes KRT1, KRT2, or KRT10 [3]. Epidermolytic ichthyosis is characterized by hyperkeratosis, erythroderma, and superficial skin fragility.

Therefore 'Epidermolytic ichthyosis' should be a child of 'keratinopathic ichthyosis'

finding 2: OMIMPS:113800 = MONDO:0957316 = Epidermolytic hyperkeratosis This OMIMPS groups:

• OMIM:113800 - Epidermolytic hyperkeratosis 1 - Gene = KRT1
• OMIM:620707 - Epidermolytic hyperkeratosis 2B, autosomal recessive - Gene = KRT10 (created/updated in OMIM on 02/07/2024)
• OMIM:620150 - Epidermolytic hyperkeratosis 2A, autosomal dominant - Gene = KRT10 = MONDO:0958184 (updated in OMIM on 02/07/2024)

To do I think epidermolytic hyperkeratosis (MONDO:0957316) and epidermolytic ichthyosis (MONDO:0007239) represent the same concept (these names are synonyms in OMIM) and these terms should be merged. The term to keep would be ‘epidermolytic ichthyosis’ (MONDO:0007239) as it is the oldest one ‘epidermolytic ichthyosis’ would be

• a child of Keratinopathic ichthyosis (ORDO:281103) = MONDO:0017266
• the parent term for
  • new term corresponding to OMIM:113800 - Epidermolytic hyperkeratosis 1 - Gene = KRT1
  • MONDO:0958184 'epidermolytic hyperkeratosis 2 (see also comment 1)

The current x-ref should be updated as below: Current MONDO:equivalentTo xref	status	To do
DOID:0081358	Represents KRT1 = epidermolytic hyperkeratosis 1	Move to new term corresponding to OMIM:113800
DOID:4603	Refers to epidermolytic hyperkeratosis	OK, stays
MESH:D017488	Refers to general Epidermolytic Ichthyosis	OK, stays
NCIT:C62569	The NCIT definition is: An autosomal dominant inherited skin disorder caused by mutations in the KRT1 and KRT10 genes. It is manifested at birth and is characterized by generalized erythema, skin blisters and skin fragility.	I think this should be move to Autosomal dominant epidermolytic ichthyosis (MONDO:0007239)
OMIM:113800	= EPIDERMOLYTIC HYPERKERATOSIS 1; EHK1 (Gene = KRT1)	Move to the new term
Orphanet:312	Autosomal dominant epidermolytic ichthyosis	move to Autosomal dominant epidermolytic ichthyosis (MONDO:0007239)
SCTID:254167000	Bullous ichthyosiform erythroderma, which is a synonym in omim	OK stays

Note that the new OMIM terms can be classified also under the existing "autosomal recessive/dominant" term

[nicolevasilevsky]

Comment 1: "epidermolytic hyperkeratosis 2"

Your plan sounds good. I suspect that Lynn + DO team will probably update their term to match OMIM, they may not be aware that OMIM split this into two terms. I'd be happy to check with them, and if they decide to split their term into two terms, we may not need to have the grouping class.

[nicolevasilevsky]

Comment 3: "Epidermolytic hyperkeratosis"

@sabrinatoro I may not be following your comment correctly but you suggested that epidermolytic hyperkeratosis (MONDO:0957316) and epidermolytic ichthyosis (MONDO:0007239) should be merged, but one of these is the OMIMPS (MONDO:0957316) and epidermolytic ichthyosis (MONDO:0007239) is part of the PS, so it should be a child of MONDO:0957316, not merged into it.

[kanems]

Comment 3: Epidermolytic hyperkeratosis @nicolevasilevsky It looks like @sabrinatoro is suggesting a new Mondo term for the OMIM child concept, thus OMIM 113800 (EPIDERMOLYTIC HYPERKERATOSIS 1) and the DOID matching concept would a NEW record; the remaining equivalentTo items are either synonymous with epid. icthyosis OR need to move to a separate (existing) Mondo ID. I agree with this reorganization approach.

All other comments/suggestions seem to be correct to me. And I think this resolves my other request on #7141 .

[nicolevasilevsky]

thanks for clarifying @kanems, sounds good to me!

[sabrinatoro]

Left to do:

• [ ] merge 'epidermolytic hyperkeratosis' (MONDO:0957316) into 'epidermolytic ichthyosis' (MONDO:0007239)
• [ ] review that the classification and IDs are correct based on comment 3
• [ ] add autosomal dominant/recessive parentage for 'epidermolytic hyperkeratosis 2' terms