ABCA12 Frameshift Deletion in Domestic Cats With Ichthyosis Fetalis

BACKGROUND: Ichthyosis fetalis (IF), also known as harlequin ichthyosis, is a rare and often fatal autosomal recessive congenital skin disorder. It is characterized by thickened, hard skin plaques and deep skin fissures that limit mobility and cause malformations of the eyes, lips and ears. Affected individuals are highly susceptible to life-threatening infections due to the disruption of the skin's protective barrier. To date, IF and its genetic basis have not been described in domestic cats. OBJECTIVES: To characterize the gross clinical, histopathological and genetic features of IF in two stray, random-bred domestic short-hair (DSH) littermates. ANIMALS: Two deceased female neonatal DSH kittens, both exhibiting sparse hair and deep fissures exposing the underlying dermis. One unrelated neonatal kitten with normal skin and hair was included as a control for comparison, along with 140 feline population samples from unrelated domestic cats of various breeds. MATERIALS AND METHODS: Gross clinical examination, histopathological analysis, whole-genome sequencing and population genotyping were performed. RESULTS: Gross clinical and histopathological evaluations confirmed a diagnosis of IF in both affected kittens. Genetic analysis identified a homozygous one base pair deletion in ABCA12, resulting in a frameshift and predicted loss of function of the encoded protein. Genotyping of 140 unrelated cats revealed that all were homozygous for the wild-type allele. CONCLUSIONS AND CLINICAL RELEVANCE: Variants in ABCA12 have been implicated previously in IF in humans, cattle and mice. This study provides the first description of IF in domestic cats and identifies a pathogenic ABCA12 frameshift variant as the likely genetic cause.

Authors: J. M. Blake, M. P. Swan and K. J. Ekenstedt Title: ABCA12 Frameshift Deletion in Domestic Cats With Ichthyosis Fetalis Full source: Vet Dermatol, 2025,Vol Document type: Journal Article
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Abstract	Source
BACKGROUND: Ichthyosis fetalis (IF), also known as harlequin ichthyosis, is a rare and often fatal autosomal recessive congenital skin disorder. It is characterized by thickened, hard skin plaques and deep skin fissures that limit mobility and cause malformations of the eyes, lips and ears. Affected individuals are highly susceptible to life-threatening infections due to the disruption of the skin's protective barrier. To date, IF and its genetic basis have not been described in domestic cats. OBJECTIVES: To characterize the gross clinical, histopathological and genetic features of IF in two stray, random-bred domestic short-hair (DSH) littermates. ANIMALS: Two deceased female neonatal DSH kittens, both exhibiting sparse hair and deep fissures exposing the underlying dermis. One unrelated neonatal kitten with normal skin and hair was included as a control for comparison, along with 140 feline population samples from unrelated domestic cats of various breeds. MATERIALS AND METHODS: Gross clinical examination, histopathological analysis, whole-genome sequencing and population genotyping were performed. RESULTS: Gross clinical and histopathological evaluations confirmed a diagnosis of IF in both affected kittens. Genetic analysis identified a homozygous one base pair deletion in ABCA12, resulting in a frameshift and predicted loss of function of the encoded protein. Genotyping of 140 unrelated cats revealed that all were homozygous for the wild-type allele. CONCLUSIONS AND CLINICAL RELEVANCE: Variants in ABCA12 have been implicated previously in IF in humans, cattle and mice. This study provides the first description of IF in domestic cats and identifies a pathogenic ABCA12 frameshift variant as the likely genetic cause.