Categories: Renal / urinary system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 613534 (gene) , 614817 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: spontaneous Fanconi syndrome, idiopathic Fanconi syndrome

Species-specific description: Information listed here was previously listed under OMIA:000366-9615 : Fanconi syndrome in Canis lupus familiaris

Mapping: In an unpublished thesis, Farias (2011) reports a genome-wide linkage study involving 59 related Basenjis comprising 22 affecteds and 37 normals, each genotyped with 325 microsatellites, that mapped this disorder to chromosome CFA3. Fine mapping of this chromosome with 29 additional microsatellites narrowed the candidate region to 2.7Mb (40,537,065 bp and 43,218,050 bp), which contains 11 identified genes.

Molecular basis: In an unpublished thesis, Farias (2011) reported whole-genome sequencing one affected Basenji and three unaffected dogs from other breeds, which eventually led to identification of a candidate causal mutation: "317 bp of exon 14 were deleted starting at the second exon14 nucleotide and extending into the 3’ untranslated region of FAN1" (the gene encoding Fanconi anemia-associated nuclease 1). This mutation showed almost perfect association with Fanconi genotype in 78 Basenjis (there being one exception, namely an unaffected dog that was homozygous for the deletion).

Clinical features: Fanconi syndrome is a rare condition in dogs which results in abnormal renal function. More specifically, it causes reduced function of the proximal convoluted tubules (Yearley et al., 2004), resulting in reduced reabsorption of water, nutrients and electrolytes from the tubular fluid and their eventual loss in urine. The clinical consequences of this disease for the animal include polyuria and polydipsia, dehydration, weight loss and muscle weakness (Yearley et al., 2004). Most cases progress to renal failure within a few years of the onset of initial clinical signs Bovée et al. (1978, PMID684432). IT thanks DVM student Harry Cahill, who provided the basis of this contribution in May 2023.

Genetic testing: The website of the Orthopedic Foundation for Animals (OFA) reports the availability of a DNA test for this disorder in the Basenji breed: https://ofa.org/diseases/?breed=BJ. To FN's knowledge, the basis of this test has not been published. It has been described, however, in a PhD thesis by Farias (2011) and a conference proceeding (Farias et al., 2012). Thanks to Mario Van Poucke and Kathy Davies for alerting FN to this thesis.

Breed: Basenji (Dog) (VBO_0200120).
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: