OMIA 001578-9796 : Immunodeficiency syndrome, SLC5A3-related in Equus caballus
Category: Immune system phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 600444 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2011
Cross-species summary: This phene was previously called 'Foal immunodeficiency syndrome in the Fell and Dales Pony' and renamed to reflect that the disease could occur in other breeds or species [30/04/2022]
Species-specific name: Foal immunodeficiency syndrome in Fell and Dales Pony; Fell pony syndrome
Species-specific symbol: FIS
Species-specific description: Fox-Clipsham et al. (2011) [Vet Rec]: "The Fell and Dales are UK pony breeds that have small populations .... . Foal immunodeficiency syndrome (FIS) is a lethal inherited disease caused by the recessive mutation of a single gene, which affects both Fell and Dales ponies and potentially other breeds that have interbred with either of these. FIS ... is characterised by progressive anaemia and severe B lymphocyte deficiency. The identification of the causal mutation for this disease led to the ... development of a DNA-based carrier test."
[IT thanks Briana Moreno, working under the guidance of Professor Ernie Bailey, for contributions to this entry in April 2022]
History: Foal immunodeficiency syndrome (FIS) was first described in 1998 as a syndrome where Fells foals developed diarrhea, cough and fail to suckle (Scholes et al., 1998). In 2009 the condition was reported in the related Dales breed (Fox-Clipsham et al., 2009) and a likely causal variant was identified in 2011 (Fox-Clipsham et al., 2011 [PLoS Genetics]).
Molecular basis: Starting with some linkage mapping, and using the full power of current genomics tools, Fox-Clipsham et al. (2011) [PLOS Genetics] identified the causal mutation for this disorder as a missense mutation in the gene encoding solute carrier family 5 (sodium/myo-inositol cotransporter), member 3 (SLC5A3), on chromosome ECA26.
A second paper by the same authors identified the variant as a C to T substitution (Fox-Clipsham et al., 2011 [Vet Rec])
Clinical features: Foals with FIS appear to be normal at birth, but present with progressive anaemia as well as diarrhea, pneumonia, or other infectious diseases within a few weeks of age (Scholes et al., 1998). After an initial response to treatment, infections reoccur (Thomas et al., 2005). Foals either die or are humanely euthanized before three months of age.
Pathology: Fox-Clipsham et al., 2011 [Vet Rec]: "The underlying pathology ... has been shown to be anaemia (Dixon et al., 2000; Richards et al., 2000), which is unrelated to blood loss or haemolysis, and a severe B lymphocyte deficiency (Thomas et al., 2003) with reduced antibody production (Thomas et al., 2005)." Reduced antibody levels in affected foals cause an inability to generate an adaptive immune response, resulting in immunodeficiency once colostrum derived antibodies decrease at 3-6 weeks of age (Dixon et al., 2000).
Prevalence: Fox-Clipsham et al. (2011) [Vet Rec] screened several breeds using the DNA-based carrier test to estimate carrier frequency for 2009/2010: "approximately 40 per cent of adult UK Fell ponies and 20 per cent of adult UK Dales ponies carried the FIS defect. ... [N]o FIS carriers were identified among the Clydesdale, Exmoor, Highland or Welsh section D samples. ... [O]f the 192 coloured horse and pony samples ... two were confirmed as carriers of FIS."
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|SLC5A3||solute carrier family 5 (sodium/myo-inositol cotransporter), member 3||Equus caballus||26||NC_009169.3 (31869233..31904230)||SLC5A3||Homologene, Ensembl, NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|158||Dales (Horse) Fell Pony (Horse)||Foal immunodeficiency syndrome in the Fell and Dales Pony||SLC5A3||missense||Naturally occurring variant||EquCab3.0||26||g.31894278C>T||c.1352C>T||p.(P451L)||NM_001247992.1; NP_001234921.1; previously listed in OMIA as g.30660224G>T in EquCab2.0, c.1337G>T and published as p.(P446L); coordinates in the table have been updated to a recent reference genome and / or transcript||2011||21750681||Briana Moreno, working under the guidance of Professor Ernie Bailey, provided genomic coordinates in EquCab3.0 in April 2022|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2011||Bailey, E. :|
|Screening for foal immunodeficiency syndrome. Vet Rec 169:653-4, 2011. Pubmed reference: 22184351. DOI: 10.1136/vr.d8118.|
|Fox-Clipsham, L.Y., Brown, E.E., Carter, S.D., Swinburne, J.E. :|
|Population screening of endangered horse breeds for the foal immunodeficiency syndrome mutation. Vet Rec 169:655, 2011. Pubmed reference: 22016514. DOI: 10.1136/vr.100235.|
|Fox-Clipsham, LY., Carter, SD., Goodhead, I., Hall, N., Knottenbelt, DC., May, PD., Ollier, WE., Swinburne, JE. :|
|Identification of a mutation associated with fatal foal immunodeficiency syndrome in the fell and dales pony. PLoS Genet 7:e1002133, 2011. Pubmed reference: 21750681. DOI: 10.1371/journal.pgen.1002133.|
|2009||Fox-Clipsham, L., Swinburne, JE., Papoula-Pereira, RI., Blunden, AS., Malalana, F., Knottenbelt, DC., Carter, SD. :|
|Immunodeficiency/anaemia syndrome in a Dales pony. Vet Rec 165:289-90, 2009. Pubmed reference: 19734561.|
|2006||Butler, CM., Westermann, CM., Koeman, JP., Sloet van Oldruitenborgh-Oosterbaan, MM. :|
|The Fell pony immunodeficiency syndrome also occurs in the Netherlands: a review and six cases. Tijdschr Diergeneeskd 131:114-8, 2006. Pubmed reference: 16514970.|
|Gardner, RB., Hart, KA., Stokol, T., Divers, TJ., Flaminio, MJ. :|
|Fell Pony syndrome in a pony in North America. J Vet Intern Med 20:198-203, 2006. Pubmed reference: 16496942.|
|Jelinek, F., Faldyna, M., Jasurkova-Mikutova, G. :|
|Severe combined immunodeficiency in a Fell pony foal. J Vet Med A Physiol Pathol Clin Med 53:69-73, 2006. Pubmed reference: 16466458. DOI: 10.1111/j.1439-0442.2006.00779.x.|
|2005||Thomas, GW., Bell, SC., Carter, SD. :|
|Immunoglobulin and peripheral B-lymphocyte concentrations in Fell pony foal syndrome. Equine Vet J 37:48-52, 2005. Pubmed reference: 15651734.|
|2003||Thomas, G.W, :|
|Immunodeficiency in Fell ponies. PhD Thesis, University of Liverpool :, 2003.|
|Thomas, GW., Bell, SC., Phythian, C., Taylor, P., Knottenbelt, DC., Carter, SD. :|
|Aid to the antemortem diagnosis of Fell pony foal syndrome by the analysis of B lymphocytes. Vet Rec 152:618-21, 2003. Pubmed reference: 12790165.|
|2001||Bell, S.C., Savidge, C., Taylor, P., Knottenbelt, D.C., Carter, S.D. :|
|An immunodeficiency in Fell ponies: a preliminary study into cellular responses Equine Veterinary Journal 33:687-692, 2001. Pubmed reference: 11770991.|
|2000||Dixon, JB., Savage, M., Wattret, A., Taylor, P., Ross, G., Carter, SD., Kelly, DF., Haywood, S., Phythian, C., Macintyre, AR., Bell, SC., Knottenbelt, DC., Green, JR. :|
|Discriminant and multiple regression analysis of anemia and opportunistic infection in Fell pony foals. Vet Clin Pathol 29:84-86, 2000. Pubmed reference: 12070803.|
|1998||Scholes, SF., Holliman, A., May, PD., Holmes, MA. :|
|A syndrome of anaemia, immunodeficiency and peripheral ganglionopathy in Fell pony foals. Vet Rec 142:128-34, 1998. Pubmed reference: 9507645.|
- Created by Frank Nicholas on 15 Jul 2011
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