OMIA 001578-9796 : Immunodeficiency syndrome, SLC5A3-related in Equus caballus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 600444 (gene)

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."

Breeds: Dales Pony, Fell Pony.

Associated gene:

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

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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 Pony Fell Pony 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

References


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.

Edit History


  • Created by Frank Nicholas on 15 Jul 2011
  • Changed by Frank Nicholas on 11 Sep 2011
  • Changed by Frank Nicholas on 08 Oct 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Imke Tammen2 on 28 Sep 2021
  • Changed by Imke Tammen2 on 29 Apr 2022
  • Changed by Imke Tammen2 on 30 Apr 2022