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Birman Hypotrichosis & Short Life Expectancy (CHSLE)
| Acronym: | CHSLE |
| Gene: | FOXN1 |
| Mutation: | c.1030_1033del |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Birman Hypotrichosis and Short Life Expectancy (CHSLE) is an autosomal recessive syndrome described in the Birman cat breed (Felis silvestris catus). Hypotrichosis is a condition of abnormal hair growth, mainly hair loss or reduction. It is a characteristic of three domestic cat breeds, Sphynx, and cats related to the Donskoy and Peterbald breeds. Birman hypotrichosis associated with short life expectancy was first time described in the 1980s, in two hairless purebred kittens in France and in the United Kingdom. Until it was already recognized many years ago, its genetic and molecular causes were not known until recently. About 50 years ago, a syndrome with similar characteristics, referred to as the ”nude” phenotype, was described in mice and later also in rats and humans. The nude phenotype is also known as the ”nude”/SCID (inherited severe combined immunodeficiency) syndrome and it combines the hypotrichosis ”nude” phenotype with an alymphoid cystic thymic dysgenesis causing T-cell immunodeficiency. CHSLE in Birmans is the first non-rodent model for its equivalent human disorder.
Congenital Hypotrichosis with Short Life Expectancy affected Birman kittens are born hairless and they develop sparse, shortened, and fragile fur. Their skin is exposed and appears as wrinkled and greasy. No behavioral changes have been noticed, and the affected kittens are as active as their littermates and they grow normally. They usually do not survive beyond 8 months. The main cause of death is respiratory or digestive infections, and some get euthanized by the owners demand due to poor quality of life. Necropsy and histopathological examination revealed an absence of the thymus and lymphocyte depletion within the spleen, Peyer’s patches, and lymph nodes.
Congenital Hypotrichosis and Short Life Expectancy in Birmans is associated with a 4 base pair deletion within the FOXN1 gene (forkhead box N1). Until adulthood, FOX proteins take part in a variety of biochemical and cellular processes, such as metabolism, aging, or cancer. FOXN1 is expressed in the epidermis and the hair bulb, within the thymus in epithelial cells, where it promotes differentiation of immature epithelial cells into functional cortical and medullary thymic epithelial cells. Medullary thymic epithelial cells are essential for the development and selection of T-cells. Mutation within the FOXN1 gene results in the expression of truncated protein and causes impaired epithelial differentiation and T-cell and thymic epithelial cell formation fails. The disorder is inherited as an autosomal recessive disorder. Affected kittens are born from healthy parents. In this case, parents are carriers (obligate heterozygotes) and therefore carry one mutant allele. Carriers have no symptoms. At conception, when mating two carriers, each kitten has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Abitbol M, Bossé P, Thomas A, Tiret L (2015): A Deletion in FOXN1 Is Associated with a Syndrome Characterized by Congenital Hypotrichosis and Short Life Expectancy in Birman Cats. PloS ONE 10(3): e0120668. doi:10.1371/journal. pone.0120668