Categories: Immune system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 600444 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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 (Horse) (VBO_0000947), Fell Pony (Horse) (VBO_0000958).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: