Independent DSG4 Frameshift Variants in Cats with Hair Shaft Dystrophy

December 2021 in “ Molecular genetics and genomics ”

Sarah Kiener, Ana Rostaher, Silvia Rüfenacht, Vidhya Jagannathan, John P. Sundberg, Monika Welle, Tosso Leeb

DSG4 gene hair shaft dystrophy desmosome formation frameshift variants homozygous variants premature stop codons loss-of-function variants

Studysummary This study found that two unrelated domestic shorthair cats had novel DSG4 gene mutations causing defective hair shafts, representing the first report of pathogenic DSG4 variants in domestic animals. Our plain-language summary of this paper — not a Tressless recommendation.

Two domestic shorthair cats with abnormal hair shaft swellings were studied, revealing clinical, histopathological, and ultrastructural features similar to the lanceolate hair phenotype in mice, which is linked to loss-of-function variants in the DSG4 gene. Genome sequencing of the affected cats and comparison with 61 control genomes identified two independent homozygous frameshift variants in the DSG4 gene, leading to premature stop codons and likely resulting in a complete loss of DSG4 function. This loss is believed to disrupt desmosome formation, which is crucial for hair shaft integrity, thus causing the observed hair shaft dystrophy. These findings suggest that the identified DSG4 variants are responsible for the condition, marking the first report of pathogenic DSG4 variants in domestic animals.

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