Ramot et al. (2014) studied 2 consanguineous Arab families with keratoderma and woolly hair, 1 of which (family 1) had previously been reported (family B) by Dja...
Ramot et al. (2014) studied 2 consanguineous Arab families with keratoderma and woolly hair, 1 of which (family 1) had previously been reported (family B) by Djabali et al. (2002). All 7 patients presented with a variable degree of striate palmoplantar keratoderma, which was generally more severe on the soles. Leukonychia was more pronounced on the fingernails than toenails. Scalp hair, body hair, eyebrows, and eyelashes were sparse, and 2 patients also exhibited woolly hair. The fifth toes showed variable degrees of pseudoainhum, ranging from external rotation to a deep sulcus at the digitoplantar fold, accompanied by a bulbous appearance of the distal toe. Symptoms appeared to be more severe with advancing age, suggesting a progressive course of the disease. The patients reported no dyspnea, syncope, or weakness, and there was no family history of early sudden death. Electrocardiography was normal in all patients, and echocardiography in the oldest patient from each family was also normal. Skin biopsy from 1 patient showed nonepidermolytic keratoderma with regular acanthosis and a normal granular layer.
▼ Molecular Genetics
In a consanguineous Arab family with palmoplantar keratoderma and woolly hair, originally reported by Djabali et al. (2002), Ramot et al. (2014) performed exome sequencing and identified homozygosity for a missense mutation in the KANK2 gene (A670V; 614610.0001). The mutation segregated with disease in this family as well as in a second Arab family that had a similar phenotype and came from the same geographic region. Screening of 100 ethnically and geographically matched controls revealed 1 individual who was heterozygous for the mutation, which was not found in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases.