Data from: A naturally occurring canine model of syndromic congenital microphthalmia

In humans, the prevalence of congenital microphthalmia is estimated to be 0.2 to 3.0 every 10,000 individuals, with non-ocular involvement reported in ~80% of cases. Inherited eye diseases have been widely and descriptively characterized in dogs, and canine models of ocular diseases have played an important role in understanding the pathophysiology and development of new therapies. A naturally occurring canine model of a syndromic disorder characterized by microphthalmia was discovered in the Portuguese Water Dogmodel of a syndromic disorder characterized by microphthalmia in the Portuguese Water Dog (PWD). As non-ocular findings included tooth enamel malformations, stunted growth, anemia, and thrombocytopenia, we hence termed this disorder Canine Congenital Microphthalmos with Hematopoietic Defects (cCMHD). GWAS and homozygosity mapping detected a 2-Mb candidate region on canine chromosome 4. Whole genome sequencing and mapping against the Canfam4 reference revealed a SINE element insertion in exon 2 of the DNAJC1 gene (g.74,274,883ins[T70]TGCTGCTTGGATT). Subsequent Real-Time PCR-based mass genotyping of a larger PWD population found the homozygous mutant genotype perfectly associated with the cCMHD phenotype. Biallelic variants in DNAJC21 are mostly found to be associated with bone marrow failure (BMF) syndrome type 3, with a phenotype that has a certain degree of overlap with Fanconi anemia, dyskeratosis congenita, Shwachman–Diamond syndrome, Diamond–Blackfan anemia, and reports of individuals showing thrombocytopenia, microdontia and microphthalmia. We therefore propose cCMHD as a naturally occurring model for DNAJC21-associated syndromes.