Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 613195 (trait) , 607511 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2015

Species-specific name: Weill-Marchesani-like syndrome; goniodysgenesis

Species-specific symbol: POAG

Species-specific description: see also OMIA 000588-9615 : Lens luxation in Canis lupus familiaris

Markers: Jeanes et al. (2019) showed that the likely causal variants for this disorder are significantly associated with height in the Petit Basset Griffon Vendeen and Shar Pei breeds, "with affected individuals being significantly shorter on average than both carriers of the mutation and clear dogs", suggesting "that selecting dogs to be of a specific short height may have increased the frequency of the mutations within these breeds".

Molecular basis: In Basset Hounds, Oliver et al. (2015) reported a likely causal mutation: "a 19 bp deletion in exon 2 that alters the reading frame and is predicted to lead to a truncated protein" (CanFam3.1 chr3:40,614,853–40,614,872). In Basset Fauve de Bretagne dogs, the same authors reported a likely causal mutation in the same gene: "a missense mutation in exon 11 causing a glycine to serine amino acid substitution ([CanFam3.1 chr3:40,808,345; c.1552G>A]; G519S) in the disintegrin-like domain of ADAMTS17 which is predicted to alter protein function". Forman et al. (2015) reported a different likely causal variant in the Petit Basset Griffon Vendéen breed, namely "a 4.96 Mb inversion . . . with breakpoints in intron 12 of ADAMTS17 (chr3:40,812,274) and a downstream intergenic region (chr3:45,768,123)". Oliver et al. (2018): "All affected [Primary open-angle glaucoma (POAG), primary lens luxation (PLL), or both] Shar-Pei were homozygous for a 6-bp deletion in exon 22 of ADAMTS17 predicted to affect the resultant protein. All unaffected Shar-Pei were heterozygous or homozygous for the wild-type allele. The variant sequence was significantly associated with affected status (diagnosis of POAG, PLL, or both). All dogs of other breeds were homozygous for the wild-type allele. The cDNA sequencing confirmed presence of the expected variant mRNA sequence in ocular tissue from the affected dog only. Gene expression analysis revealed a 4.24-fold decrease in the expression of ADAMTS17 in ocular tissue from the affected dog."

Breeds: Basset Fauve de Bretagne (Dog) (VBO_0200125), Basset Hound (Dog) (VBO_0200126), Chinese Shar-Pei (Dog) (VBO_0200351), Petit Basset Griffon Vendeen (Dog) (VBO_0201009).
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: