NTR Pelger-Huet anomaly

[diatomsRcool]

If this is a request for a new term, please provide us with the following information.

1. Preferred term label (e.g., asplenia) Pelger-Huet anomaly

2. Synonyms (e.g., absent spleen)

3. Textual definition (the definition should be understandable even for non-specialists. Include a PubMed ID or URL(s) to refer to any relevant article(s) that provides information about the suggested term).

nuclei of several types of white blood cells (neutrophils and eosinophils) have unusual shape (bilobed, peanut or dumbbell-shaped) and unusual structure (coarse and lumpy).

4. Any additional notes to clarify the meaning or use of the term. Please provide a PubMed ID or URL(s) for the source of this information.

Seen in dogs and humans PMID: 2649629

5. Suggested parent term (Please look in the hierarchy of the MP using the MP Browser or other browsers such as OLS and find the place in the MP where the new term best fits)

abnormal neutrophil morphology and abnormal eosinophil morphology

6. If you would like a nanoattribution, please indicate your ORCID id or provide a label such as MGI:sbello (organization, first initial-last name)

0000-0002-5034-2637

[sbello]

This HPO term http://www.informatics.jax.org/vocab/hp_ontology/HP:0011447 has Pelger-Huet anomaly as a synonym but applies only to neutrophils.

DO has the term as well https://disease-ontology.org/?id=DOID:9631 defined as "A hematopoietic system disease characterized by white blood cells with unusually shaped nuclei that has_material_basis_in heterozygous mutation in LBR on chromosome 1q42.12. " so all white blood cells not just neutrophils and eosinophils

DO references https://pubmed.ncbi.nlm.nih.gov/12118250/ which states "Pelger-Huët anomaly (PHA; OMIM *169400) is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes."

MESH has "Autosomal dominant anomaly characterized by abnormal ovoid shape GRANULOCYTE nuclei and their clumping chromatin"

OMIM record mentions neutrophils, granulocytes, and leukocytes.

NCI record has "defects in the neutrophil lobulation"

Will continue to look into this. We may be better off going with individual terms for each cell type with a broad synonym of Pelger-Huet anomaly, similar to what HPO has.

[sbello]

Additional reference https://pubmed.ncbi.nlm.nih.gov/22338047/ "The Pelger-Huët anomaly (PHA) is a recognized morphologic variant affecting all granulocytes but is most evident in polymorphonuclear neutrophils (PMNs)."

" It is now known that heterozygous mutations of LBR result in hyposegmented PMN nuclei known as PHA." Table 1 has list of features of PHA and pseudo-PHA

So, it seems like the salient features are:

• hyposegmented, symmetrical nuclei
• more condensed chromatin

Just having hyposegmentation would not differentiate between PHA and pseudo-PHA, we could add new terms for both symmetrical hyposegmentation and increased chromatin condensation.

PMID:24255920 describes mouse model with pseudo-PHA in neutrophils

a number of existing annotations refer to hypersegmented nuclei in neutrophils

MGI has one model of PHA - mentions both neutrophil and eosinophil segmentation (PMID:12490533)

[sbello]

Proposal add terms for: abnormal granulocyte nuclear morphology abnormal neutrophil nuclear morphology abnormal neutrophil nuclear segmentation decreased neutrophil nuclear segmentation symmetrical hyposegmentation of neutrophil nuclei (related synonym Pelger-Huet anomaly) asymmetrical hyposegmentation of neutrophil nuclei increased neutrophil nuclear segmentation abnormal neutrophil chromatin condensation increased neutrophil chromatin condensation decreased neutrophil chromatin condensation abnormal eosinophil nuclear morphology abnormal eosinophil nuclear segmentation decreased eosinophil nuclear segmentation (related synonym Pelger-Huet anomaly) increased eosinophil nuclear segmentation

[sbello]

@diatomsRcool How critical is it for you to have the combined term? My preference would be to follow the proposal above with separate terms for the neutrophils and eosinophils that have a synonym for PHA. This would avoid some of the confusion of the variable usage and presentation of PHA but would mean you would need to annotate to more terms.

[diatomsRcool]

I will defer to @hughesk83 who is the specialist here

[hughesk83]

I think this looks good but I am not sure if we should have chromatin condensation also included. I think that is more subjective and the better characterized phenotype is the hyposegmentation. I think having separate terms for neuts and eos is a good suggestion.

[sbello]

I'm fine not dealing with the chromatin terms. I'll try to get the rest in in the next week.

[sbello]

Added terms:

MP:0021171 | abnormal granulocyte nuclear morphology MP:0021172 | abnormal neutrophil nuclear morphology MP:0021173 | abnormal neutrophil nuclear segmentation MP:0021174 | decreased neutrophil nuclear segmentation MP:0021175 | symmetrical hyposegmentation of neutrophil nuclei MP:0021176 | asymmetrical hyposegmentation of neutrophil nuclei MP:0021177 | increased neutrophil nuclear segmentation MP:0021178 | abnormal eosinophil nuclear morphology MP:0021179 | abnormal eosinophil nuclear segmentation MP:0021180 | decreased eosinophil nuclear segmentation MP:0021181 | increased eosinophil nuclear segmentation

[sbello]

@diatomsRcool I've added all the terms but the MP build is currently failing due (I think) to unrelated issues. We're looking into the issue and I'll let you know when the terms are available for use.

[sbello]

Build is back up, terms should be available on Monday