In other species: domestic cat

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: 2010

Species-specific name: Primary lens luxation; isolated canine ectopia lentis; luxatio lentis

Species-specific symbol: PPL

Species-specific description: see also OMIA 001976-9615 : Glaucoma, primary open angle, ADAMTS17-related in Canis lupus familiaris

Mapping: Sargan et al. (2007) conducted a genome scan with 364 microsatellites on "23 PLL-affected miniature bull terriers, together with an equal number of obligate PLL carriers with no luxation, and also 23 PLL-affected Lancashire heeler, with an equal number of obligate carriers with no luxation". A linkage analysis highlighted "a 6.3-Mbp region in the central part of chromosome 3". By conducting a GWAS on 28 affected and 20 control Jack Russell Terriers, each genotyped with the CanineSNP20 BeadChip, Farias et al. (2010) highlighted the same region on chromosome CFA3 as identified by Sargan et al. (2008). Subsequent fine-mapping narrowed the region to a 664kb segment harbouring the positional candidate gene ADAMTS17.

Molecular basis: By sequencing the positional candidate gene ADAMTS17, Farias et al. (2010) identified the causal mutation as "a G→A transition at c.1473+1, which destroys the splice donor recognition site in intron 10". Gould et al. (2011) "screened 121 dogs of 30 different breeds that were clinically affected with PLL for the previously described ADAMTS17 mutation [OMIA variant:365]. ... In addition to the three previously reported breeds we identified at least one dog of each of 14 different breeds that was homozygous for the ADAMTS17 mutation and clinically affected (Australian Cattle dog, Chinese crested dog, Jagdterrier [also known as the German hunt terrier], Parson Russell terrier, Patterdale terrier, Rat terrier, Sealyham terrier, Tenterfield terrier, Tibetan terrier, Toy fox terrier, Volpino Italiano, Welsh terrier, Wire-haired fox terrier, Yorkshire terrier). 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."

Clinical features: The clinical features associated with primary lens luxation (PLL) are changes to eye lens stability in both eyes, with varying severity of clinical signs associated with each eye. PLL typically goes undetected until the lens displaces in one eye. Dogs typically present with concurrent partial lens displacement of the other eye, which progresses into full displacement weeks to months later (Farias et al., 2010; Colitz & O’Connell, 2015). The lens usually moves anteriorly causing disruption to the pupil and draining mechanism in the eye, leading to acute glaucoma (Gould et al., 2011; Gharahkhani et al., 2015). IT thanks DVM student Zoe Levesque, who provided the basis of this contribution in May 2023.

Prevalence: Tzouganakis et al. (2022) genotyped 82 Portuguese Podengo dogs in the UK genotyping for the ADAMTS17:c.1473+1G>A mutation. The allele frequency for the variant was estimated calculated as 0.09.

Breeds: American Toy Terrier (Dog) (VBO_0200057), Australian Cattle Dog (Dog) (VBO_0200088), Border Collie (Dog) (VBO_0200193), Brittany Spaniel (Dog) (VBO_0200239), Chinese Crested (Dog) (VBO_0200345), Chinese Shar-Pei (Dog) (VBO_0200351), German Hunting Terrier (Dog) (VBO_0200568), German Pinscher (Dog) (VBO_0201454), German Spitz (Dog) (VBO_0200585), Jack Russell Terrier (Dog) (VBO_0200724), Lancashire Heeler (Dog) (VBO_0200808), Miniature Bull Terrier (Dog) (VBO_0200882), Parson Russell Terrier (Dog) (VBO_0200987), Patterdale Terrier (Dog) (VBO_0200990), Portuguese Podengo (Dog) (VBO_0201067), Rat Terrier (Dog) (VBO_0201125), Sealyham Terrier (Dog) (VBO_0201200), Tenterfield Terrier (Dog) (VBO_0201342), Tibetan Terrier (Dog) (VBO_0201353), Toy Fox Terrier (Dog) (VBO_0201361), Volpino Italiano (Dog) (VBO_0201390), Welsh Terrier (Dog) (VBO_0201412), Wire Fox Terrier (Dog) (VBO_0201424), Yorkshire Terrier (Dog) (VBO_0201448).
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: