• hHb3
• hair loss
• monilethrix
• type II hair keratin

Monilethrix (MIM #158 000) is an autosomal dominant hair disorder that can cause scarring alopecia in affected individuals.¹ Nail changes and keratosis pilaris of the skin of neck and arms have also been described. The hallmark hair abnormality in monilethrix is a beading of the hair shaft caused by periodic narrowing with the nodes separated by about 0.7 mm. The cause of the beading is unknown. The expression of monilethrix is variable.² In mild cases, dystrophic hairs may be found only on the occiput, but severely affected individuals may suffer complete alopecia.

Most cases described so far are associated with mutations in the type II (basic) trichocyte keratin genes hHb1 and hHb6.^{2,3,4,5,6,7,8,9,10,11,12,13,14} Both genes have a mutational hotspot in the region coding for the helix termination motif. Most mutations seem to affect the same residues—glutamic acids at positions 413 and 402.^3,6,10,15 Mutations affecting the helix initiation motif have also been found.⁷ From the phenotype, it is apparent that hHb1 and hHb6 are major hair cortex keratins. A third type II trichocyte keratin, hHb3, is expressed in much the same pattern as hHb1.¹⁶ From this, it may be expected that mutations of hHb3 may cause monilethrix as well. However, mutations in this gene have so far not been described.

We analysed three patients suffering from monilethrix for the presence of mutations in hHb1, hHb3, and hHb6. In one patient, we found a heterozygous missense mutation in hHb3 causing the substitution of a glutamic acid by a lysine at position 407 in the helix termination motif (E407K). This mutation corresponds to the E402K substitution in hHb1 and hHb6, clearly defining this particular residue as a trichocyte keratin …