In other species: dog , domestic cat , tiger , puma , pig , llama , taurine cattle , sheep , rabbit , golden hamster , yellow-crowned parrot

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 109400 (trait) , 112240 (trait) , 123155 (trait) , 209970 (trait) , 236600 (trait) , 236635 (trait) , 236640 (trait) , 236660 (trait) , 236670 (trait) , 236690 (trait) , 273730 (trait) , 276950 (trait) , 307000 (trait) , 307010 (trait) , 314390 (trait) , 123155 (trait) , 600257 (trait) , 600559 (trait) , 600991 (trait) , 615181 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2015

Cross-species summary: Enlargement of the cranium caused by accumulation of fluid.

Inheritance: Ducro et al. (2015) reported that "All 16 available cases and none of the controls were homozygous for the mutation, and all 17 obligate carriers (= dams of cases) were heterozygous."

Mapping: A genome-wide association study of hydrocephalus in 13 cases and 69 controls using 29,720 SNPs indicated the involvement of a region on ECA1" [from 61 to 87 Mb] (Ducro et. al, 2015). {Adapted by FN from text provided by Meredith O’Connell, working under the supervision of Professor Ernie Bailey; 24 April 2019}

Molecular basis: Ducro et al. (2015) reported that "Next generation DNA sequence analysis of 4 cases and 6 controls of gene exons within the [candidate] region [see Mapping section] revealed a [nonsense] mutation in β-1,3-N-acetylgalactosaminyltransferase 2 (B3GALNT2) as the likely cause of hydrocephalus in Friesian horses. The nonsense mutation XM_001491545 c.1423C>T corresponding to XP_001491595 p.Gln475* was identical to a B3GALNT2 mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus.” {Adapted by FN from text provided by Meredith O’Connell, working under the supervision of Professor Ernie Bailey; 24 April 2019} Kolb and Klein (2019) reported the same likely causal variant in a congenital hydrocephalic Belgian draft horse.

Clinical features: “Hydrocephalus is defined as ‘an active distension of the ventricular system of the brain resulting from inadequate passage of cerebrospinal fluid (CSF) from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation . . .’ Hydrocephalus can be acquired, e.g. due to infection or trauma, or can be hereditary in nature. To our best knowledge, no clear cases of a proven acquired hydrocephalus in horses have been reported in scientific literature. Different types of hydrocephalus have been identified based on the underlying mechanisms: communicating (increased production or impaired CSF absorption) or non-communicating (obstruction in CSF flow) . . . . Also, hydrocephalus can be internal or external, that is an accumulation of CSF respectively within or outside the ventricles of the brain. In horses, both external and internal hydrocephalus . . . have been diagnosed” (Ducro et. al, 2015). {Text provided by Meredith O’Connell, working under the supervision of Professor Ernie Bailey; 24 April 2019}

Prevalence: “Out of 60 stallions that were genotyped using a commercially available DNA test based on the B3GALNT2 mutation, 8 (13.3 %) were carrier of the allele T. Out of 805 broodmares, 139 (17.3 %) were also carrier.” (Ducro et al., 2015). As the authors reported, this gives a frequency of the likely causal variant of 8.5%. {Adapted by FN from text provided by Meredith O’Connell, working under the supervision of Professor Ernie Bailey; 24 April 2019}

Breeds: Belgian Draft (Horse) (VBO_0000915), Friesian (Horse) (VBO_0000969), Warmblood (Horse) (VBO_0017483).
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: