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A deletion in FOXN1 is associated with a syndrome characterized by congenital hypotrichosis and short life expectancy in Birman cats.

Abitbol M, Bossé P, Thomas A, Tiret L - PLoS ONE (2015)

Bottom Line: This 4-bp deletion was associated with the syndrome when present in two copies.Our results enlarge the panel of recessive FOXN1 loss-of-function alleles described in mammals.A DNA test is available; it will help owners avoid matings at risk and should prevent the dissemination of this morbid mutation in domestic felines.

View Article: PubMed Central - PubMed

Affiliation: U955 IMRB, INSERM, Équipe 10, Créteil, France; BNMS-Génétique Médicale Comparée des Affections Neuromusculaires, École nationale vétérinaire d'Alfort, Maisons-Alfort, France.

ABSTRACT
An autosomal recessive syndrome characterized by congenital hypotrichosis and short life expectancy has been described in the Birman cat breed (Felis silvestris catus). We hypothesized that a FOXN1 (forkhead box N1) loss-of-function allele, associated with the nude phenotype in humans, mice and rats, may account for the syndrome observed in Birman cats. To the best of our knowledge, spontaneous mutations in FOXN1 have never been described in non-human, non-rodent mammalian species. We identified a recessive c.1030_1033delCTGT deletion in FOXN1 in Birman cats. This 4-bp deletion was associated with the syndrome when present in two copies. Percentage of healthy carriers in our French panel of genotyped Birman cats was estimated to be 3.2%. The deletion led to a frameshift and a premature stop codon at position 547 in the protein. In silico, the truncated FOXN1 protein was predicted to lack the activation domain and critical parts of the forkhead DNA binding domain, both involved in the interaction between FOXN1 and its targets, a mandatory step to promote normal hair and thymic epithelial development. Our results enlarge the panel of recessive FOXN1 loss-of-function alleles described in mammals. A DNA test is available; it will help owners avoid matings at risk and should prevent the dissemination of this morbid mutation in domestic felines.

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Related in: MedlinePlus

Pedigree-tree of a Birman cat family segregating hypotrichosis with reduced life span.Circles represent females, squares represent males. Affected kittens are depicted with fully filled symbols and the proband shown with an arrow. Healthy carriers are depicted with two-toned symbols. Red symbols represent cats with only phenotyping data (no DNA available); black symbols represent cats with phenotyping and genotyping data. For example, healthy cats with a N/del genotype are depicted with a two-toned black symbol. Common male ancestors of the two affected kittens are contoured in blue. This pedigree-tree suggests an autosomal recessive inheritance of the syndrome.
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pone.0120668.g002: Pedigree-tree of a Birman cat family segregating hypotrichosis with reduced life span.Circles represent females, squares represent males. Affected kittens are depicted with fully filled symbols and the proband shown with an arrow. Healthy carriers are depicted with two-toned symbols. Red symbols represent cats with only phenotyping data (no DNA available); black symbols represent cats with phenotyping and genotyping data. For example, healthy cats with a N/del genotype are depicted with a two-toned black symbol. Common male ancestors of the two affected kittens are contoured in blue. This pedigree-tree suggests an autosomal recessive inheritance of the syndrome.

Mentions: Both kittens were born hairless (e.g. in Fig. 1C) and developed sparse, shortened and fragile fur (Fig. 1D). Their skin was wrinkled and looked greasy. Besides, they were as active as their littermates and grew normally. A thorough pedigree analysis allowed to identify a common ancestor born in 1977, recognized by breeders to have produced several hairless kittens (Fig. 2). Pedigree data were consistent with an autosomal recessive inheritance pattern for this syndrome combining hypotrichosis with short life expectancy (Fig. 2).


A deletion in FOXN1 is associated with a syndrome characterized by congenital hypotrichosis and short life expectancy in Birman cats.

Abitbol M, Bossé P, Thomas A, Tiret L - PLoS ONE (2015)

Pedigree-tree of a Birman cat family segregating hypotrichosis with reduced life span.Circles represent females, squares represent males. Affected kittens are depicted with fully filled symbols and the proband shown with an arrow. Healthy carriers are depicted with two-toned symbols. Red symbols represent cats with only phenotyping data (no DNA available); black symbols represent cats with phenotyping and genotyping data. For example, healthy cats with a N/del genotype are depicted with a two-toned black symbol. Common male ancestors of the two affected kittens are contoured in blue. This pedigree-tree suggests an autosomal recessive inheritance of the syndrome.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363148&req=5

pone.0120668.g002: Pedigree-tree of a Birman cat family segregating hypotrichosis with reduced life span.Circles represent females, squares represent males. Affected kittens are depicted with fully filled symbols and the proband shown with an arrow. Healthy carriers are depicted with two-toned symbols. Red symbols represent cats with only phenotyping data (no DNA available); black symbols represent cats with phenotyping and genotyping data. For example, healthy cats with a N/del genotype are depicted with a two-toned black symbol. Common male ancestors of the two affected kittens are contoured in blue. This pedigree-tree suggests an autosomal recessive inheritance of the syndrome.
Mentions: Both kittens were born hairless (e.g. in Fig. 1C) and developed sparse, shortened and fragile fur (Fig. 1D). Their skin was wrinkled and looked greasy. Besides, they were as active as their littermates and grew normally. A thorough pedigree analysis allowed to identify a common ancestor born in 1977, recognized by breeders to have produced several hairless kittens (Fig. 2). Pedigree data were consistent with an autosomal recessive inheritance pattern for this syndrome combining hypotrichosis with short life expectancy (Fig. 2).

Bottom Line: This 4-bp deletion was associated with the syndrome when present in two copies.Our results enlarge the panel of recessive FOXN1 loss-of-function alleles described in mammals.A DNA test is available; it will help owners avoid matings at risk and should prevent the dissemination of this morbid mutation in domestic felines.

View Article: PubMed Central - PubMed

Affiliation: U955 IMRB, INSERM, Équipe 10, Créteil, France; BNMS-Génétique Médicale Comparée des Affections Neuromusculaires, École nationale vétérinaire d'Alfort, Maisons-Alfort, France.

ABSTRACT
An autosomal recessive syndrome characterized by congenital hypotrichosis and short life expectancy has been described in the Birman cat breed (Felis silvestris catus). We hypothesized that a FOXN1 (forkhead box N1) loss-of-function allele, associated with the nude phenotype in humans, mice and rats, may account for the syndrome observed in Birman cats. To the best of our knowledge, spontaneous mutations in FOXN1 have never been described in non-human, non-rodent mammalian species. We identified a recessive c.1030_1033delCTGT deletion in FOXN1 in Birman cats. This 4-bp deletion was associated with the syndrome when present in two copies. Percentage of healthy carriers in our French panel of genotyped Birman cats was estimated to be 3.2%. The deletion led to a frameshift and a premature stop codon at position 547 in the protein. In silico, the truncated FOXN1 protein was predicted to lack the activation domain and critical parts of the forkhead DNA binding domain, both involved in the interaction between FOXN1 and its targets, a mandatory step to promote normal hair and thymic epithelial development. Our results enlarge the panel of recessive FOXN1 loss-of-function alleles described in mammals. A DNA test is available; it will help owners avoid matings at risk and should prevent the dissemination of this morbid mutation in domestic felines.

Show MeSH
Related in: MedlinePlus