Birman Hypotrichosis and Short Life Expectancy (CHSLE)
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 from Donskoy and Peterbald breed. Birman hypotrichosis associated with short life expectancy was first time described in the 1980’s, 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 syndrom with similar characteristics, referred to as ”nude” phenotype, was described in mice and later also in rats and humans. 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.
Characteristics and Symptoms
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. 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 reveals an absence of the thymus and lymphocyte depletion within spleen, Peyer’s patches and lymph nodes.
Congenital Hypotrichosis and Short Life Expectancy in Birmans is associated with a 4 base pair deletion within 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 epithelian cells, where it promotes differentiation of immature epithelial cells into functional cortical and medullary thymic epithelial cells. Medullary thymic epithelial cells are essential for development and selection of T-cells.
Mutation within FOXN1 gene results in expression of truncated protein and causes impaired epithelial differentiation and T-cell and thymic epithelial cells 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.
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