Add ring chromosome syndrome(s)

[allenbaron]

Orphanet lists quite a few ring chromosome syndromes. In a review about syndromes associated with ring formation, Yip[^1] states:

Severe growth deficiency without major malformations is a common finding in the ring chromosome carrier. This phenotype associated with ring behaviour and mitotic instability and independent of the chromosome involved has been termed the “ring syndrome”.

Among those listed at least chromosome 14 and 20 can be found elsewhere:

• ring chromosome 14 syndrome
  • OMIM: https://www.omim.org/entry/616606
  • MedlinePlus: https://medlineplus.gov/genetics/condition/ring-chromosome-14-syndrome/
• ring chromosome 20 syndrome
  • MedlinePlus: https://medlineplus.gov/genetics/condition/ring-chromosome-20-syndrome/

On MedlinePlus ring chromosomes are also mentioned in a number of other chromosome records (see search results), including at least 1-7, 9-12, 15, 17-19, 21, and 22. There are also a number of specific disease records in this search in which ring chromosomes appear to be occasional causes for which suggests the need for caution in creating these diseases (examples: Wolf-Hirschhorn syndrome and Dermatofibrosarcoma protuberans. This comment from Yip[^1] also suggests caution:

Phenotypes associated with ring chromosomes are highly variable as apart from any deletion caused by ring formation, imbalances from ring instability can also occur.

We should take care not to create these unless we are certain they are used in clinical practice.

[^1]: Yip MY. Autosomal ring chromosomes in human genetic disorders. Transl Pediatr. 2015 Apr;4(2):164-74. doi: 10.3978/j.issn.2224-4336.2015.03.04. PMID: 26835370; PMCID: PMC4729093.

[allenbaron]

I think there is enough evidence to create syndromes for chromosomes 14 (refs: OMIM, MedlinePlus) and 20 (refs: MedlinePlus, paper by Yip above, and [^1][^2]) at the very least.

I also think it makes sense to create a grouping parent to capture cases where there is no clearly defined syndrome for a given chromosome. Additionally, we should avoid including diseases as children that are only occasionally caused by the formation of a ring chromosome (e.g. diseases caused by chromosomal deletion, where in some cases a ring chromosome also forms). I'll do a bit more research on this and determine what a good name for the parent term would be. It would most likely be a child of 'chromosomal disease' (DOID:0080014).

[^1]: Peron A, Catusi I, Recalcati MP, Calzari L, Larizza L, Vignoli A, Canevini MP. Ring Chromosome 20 Syndrome: Genetics, Clinical Characteristics, and Overlapping Phenotypes. Front Neurol. 2020 Dec 8;11:613035. doi: 10.3389/fneur.2020.613035. PMID: 33363513; PMCID: PMC7753021. [^2]: James WD, Roth R, Fitzgerald M. Ring 20 syndrome: A call to action. Epilepsia. 2024 Apr;65(4):1147-1148. doi: 10.1111/epi.17941. Epub 2024 Mar 5. PMID: 38441298.

[lschriml]

definition: A ring chromosome is an aberrant chromosome whose ends have fused together to form a ring.

-- may be up to 23 subtypes: https://en.wikipedia.org/wiki/Ring_chromosome

-- Agreed, please go ahead and add this category and the subtypes that have literature support. Cheers, Lynn

[allenbaron]

One more cautionary note. We should be sure to avoid adding diseases that are NOT diseases. I happened across Mondo's 'ring chromosome disorder' (MONDO:0700091) which cross-references 'Supernumerary Circular Chromosome' in the NCI Thesaurus (NCI:C3360) which is a 'Molecular Abnormality' and not a 'Disease, Disorder or Finding'. The children of this disease are also primarily just a list of the ring chromosomes.

[lschriml]

Let's add a HP axiom, if possible for the chromosomal structural variation.

On Thu, Sep 19, 2024 at 2:38 PM J. Allen Baron @.***> wrote:

One more cautionary note. We should be sure to avoid adding diseases that are NOT diseases. I happened across Mondo's 'ring chromosome disorder' ( MONDO:0700091 http://purl.obolibrary.org/obo/MONDO_0700091) which cross-references 'Supernumerary Circular Chromosome' in the NCI Thesaurus ( NCI:C3360 https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C3360) which is a 'Molecular Abnormality' and not a 'Disease, Disorder or Finding'. The children of this disease are also primarily just a list of the ring chromosomes.

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[allenbaron]

Did you have something in mind from HP? I don't see anything that would work. The closest thing I found there was 'Chromosome breakage' (HP:0040012).

Would this be an appropriate axiom: disease and ('has material basis in' some ring_chromosome)

Supporting information:

• ring_chromosome(SO:1000045) is a descendant of chromosome_structure_variation (SO:1000183).
• disease and ('has material basis in' some chromosome_structure_variation) is the EQ axiom for what would be the parent of this term, 'chromosomal disease' (DOID:0080014)

Is there possibly a better relationship term for this axiom?

disease has basis in (RO:0004019)

Used in the DO but it's not defined so it's not really clear to me how it's supposed to be used.

One of its children is 'disease arises from alteration in structure' (RO:0004030) which seems like it would be a perfect fit in this scenario but the definition of that term seems to suggest the target of the relation should be the structure that is changed not the structure it is changed into, so maybe chromosome & not ring chromosome in this case.

A relationship between a disease and an anatomical structure where the material basis of the disease is some pathological change in the structure. Anatomical structure includes cellular and sub-cellular entities, such as chromosome and organelles.

The axiom 'disease has basis in' some gene which exists in the DO kind of supports this interpretation for 'disease has basis in', which means it probably wouldn't be the axiom to use here.

process has causal agent (RO:0002608)

~This term has no definition but logically it is defined as the inverse of 'causal agent in process' (RO:0002500), which has the definition:~

~A relationship between a material entity and a process where the material entity has some causal role that influences the process~

~A ring chromosome is a material entity and disease is a process. The existence of the ring chromosome has a causal role that influences the process. Could this work?~

Nevermind... I just remembered that disease is not a "process" but a "disposition" to undergo pathological "processes", which makes it a "realizable entity" 😮‍💨. This one won't work.

New RO term?

It seems like what we need to cover this situation is an RO term that indicates a process occurs because some material entity is brought into existence by a change in another. 'disease arises from alteration in structure' seems so close but it won't work here because it doesn't specify HOW the chromosome is changed, which is essential here. Maybe we should build a more complex axiom with 'disease has basis in' where the object is itself an axiom stating that ring chromosome derives from chromosome. I imagine there's a relation for that.