Mutation E402K of the hHb6 in a Chinese Han family with monilethrix

ARTICLE

Auteur(s) : Shi-de Zhang, Jin Meng, Jing-jun Zhao, Wei Tian

Department of Dermatology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, China

The proband was a 6-year-old girl who presented with short, weathered, and thinly implanted hair and pronounced follicular hyperkeratosis over the entire scalp. At birth her scalp hair looked normal. But after about one month her hair became shorter and shorter and some small papules emerged. Her nails and teeth were normal, and she did not have any other complications. Her father was also affected. He had had almost the same history of hair disorder when he was a child. He had obvious re-growth of normal hair at puberty. But now we found he had hair loss at the occiput and the nape of the neck and mild follicular hyperkeratosis. The other four members of the family were not affected. Under a light microscope, the proband and her father showed typical moniliform hair with periodic widening and narrowing. Sequence analysis revealed that there was a missense mutation, c.1204G>A, in the hHb6 gene in the 2 affected members. No mutation was detected in the healthy members in this family or 50 normal controls. This mutation led to a substitution of glutamic acid by lysine at codon402 (E402K).

The hotspots of keratin mutations are usually in the helix initiation (1A) or termination (2B) motifs [1]. Up to now, seven different types of mutations have been detected to be associated with monilethrix (table 1). In these three keratins (hHb1, hHb3 and hHb6), the HTM was the most mutated region while a few HIM mutations occurred only in the hHb6 keratin. Among the hHb6 mutations, the non-conservative E413K substitution was by far the most frequent mutation, followed by the conservative E413D and the non-conservative E402K substitutions. But in the hHb1 keratin, E402K mutations were mostly found. Only one disease-causing hHb3 mutation has been detected in a single monilethrix family [2].
Table 1 Different mutations reported in monilethrix

In China several monilethrix pedigrees have been reported and another 2 gene defects have been studied in recent years. Only one kind of mutation: c.1204G>A (p. E402K) was found in all pedigrees examined so far (table 1). One pedigree that was previously reported originated in the center of China (Henan Province) and was a four-generation family with 9 affected members [3]. Another monilethrix pedigree was found in the middle of China (Hubei Province), this was a two-generation family and only two affected individuals (daughter and mother) [4]. The pedigree we present is the first reported in southeast China (Fujian Province). All these affected individuals have different severities of clinical features, from only involving the occiput and the nape of the neck, the entire scalp, to involving the eyebrows, armpit hair, with or without follicular keratosis. No abnormal nail, eyebrows and eyelashes were found. But same mutation has been recognized in all affected members. So genotype/phenotype correlation was not obvious in the Chinese Han population. These findings coordinate with other reported cases [5, 6]. On the other hand, mutations have been found all in affected individuals and no mutation was found in normal members among these 3 pedigrees. This is not same as other original pedigrees [5]. One reason may be the limited number of families studied in China. Other genetic or environmental factors may also play a role in monilethrix.

Acknowledgments

References

2 van Steensel MA, Steijlen PM, Bladergroen RS, Vermeer M, van Geel M. A missense mutation in the type II hair keratin hHb3 is associated with monilethrix. J Med Genet 2005; 42: e19.

3 LZ Li JG, Wang YP, Liao SX, Zhang SM. Detection of mutation of hHb6 in a Chinese pedigree of Monilethrix. Zhonghua Pi Fu Ke Za Zhi 2006; 39: 374-6.

4 Feng AP, Liu P, Yang T. Analysis of human hair basic keratin 6 gene mutation in a Chinese Han family with monilethrix. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2008; 25: 141-4.

5 Korge BP, Hamm H, Jury CS, et al. Identification of novel mutations in basic hair keratins hHb1 and hHb6 in monilethrix: implications for protein structure and clinical phenotype. J Invest Dermatol 1999; 113: 607-12.

6 Winter H, Labreze C, Chapalain V, et al. A variable monilethrix phenotype associated with a novel mutation, Glu402Lys, in the helix termination motif of the type II hair keratin hHb1. J Invest Dermatol 1998; 111: 169-72.

* These authors contributed equally to this work. Corresponding author: Jing-jun Zhao