Uncombable Hair Syndrome 2

A number sign (#) is used with this entry because of evidence that uncombable hair syndrome-2 (UHS2) is caused by homozygous mutation in the TGM3 gene (600238) on chromosome 20p13. One such patient has been reported.

Description

Uncombable hair syndrome is characterized by silvery, blond, or straw-colored scalp hair that is dry, frizzy, and wiry, has a characteristic sheen, stands away from the scalp in multiple directions, and is impossible to comb. This hair shaft disorder occurs in children and improves with age. The hair growth rate can range from slow to normal (summary by U. Basmanav et al., 2016).

For a general phenotypic description and a discussion of genetic heterogeneity of UHS, see UHS1 (191480).

Clinical Features

Kilic et al. (2013) reported a 24-year-old Turkish man, born of consanguineous parents, who had yellowish, dry, frizzy hair that projected outward. His mother stated that his hair had that texture since infancy, was slow growing, and was always hard to comb. Neither alopecia nor hypotrichosis was present, and there was no evidence of scalp abnormalities. Eyebrows, eyelashes, and body hair were not involved. Mucosae, teeth, nails, and sweating were normal. Light microscopic examination of the hairs revealed canal-like longitudinal depressions and, on trichoscopy, a longitudinal grooving was also detected. The diagnosis of UHS was confirmed by scanning electron microscopy (SEM), which showed shallow grooving along the entire length of the hairs examined. Further work-up demonstrated bilateral juvenile cataract.

Molecular Genetics

By whole-exome sequencing in the Turkish patient with uncombable hair syndrome reported by Kilic et al. (2013), who did not have a mutation in the PADI3 gene (606755), U. Basmanav et al. (2016) identified a homozygous nonsense mutation (Q451X; 600238.0001) in the TGM3 gene. Functional experiments in HaCaT and HEK293T cells showed that the mutations led to reduced enzymatic activity.