Monilethrix: a novel mutation (Glu402Lys) in the helix termination motif and the first causative mutation (Asn114Asp) in the helix initiation motif of the type II hair keratin hHb6.

@article{Winter1999MonilethrixAN,
  title={Monilethrix: a novel mutation (Glu402Lys) in the helix termination motif and the first causative mutation (Asn114Asp) in the helix initiation motif of the type II hair keratin hHb6.},
  author={Hermelita Winter and Robin Dawn Clark and C Tarras-Wahlberg and Michael A. Rogers and Juergen Schweizer},
  journal={The Journal of investigative dermatology},
  year={1999},
  volume={113 2},
  pages={
          263-6
        }
}
Monilethrix, a rare human hair disorder with autosomal dominant transmission, can be caused by mutations in hair keratins. Up to now, causative mutations have only been found in two type II cortex keratins, hHb6 and hHb1. In these hair keratins, the helix termination motif, HTM, was the only site in which mutations were located. The most frequent mutation, which has been found in 22 cases, was a Glu413Lys substitution in hHb6, whereas other mutations, i.e., hHb6 Glu413Asp, hHb1 Glu413Lys, and… 
Recurrent missense mutations in the hair keratin gene hHb6 in monilethrix
TLDR
Two unrelated families from Russia and Colombia with monilethrix are investigated and two missense mutations in hHb6 are found, extending the body of evidence implicating recurrent hHhb6 and hHB1 mutations in monilehrix families from around the world.
A missense mutation in the type II hair keratin hHb3 is associated with monilethrix
TLDR
The hallmark hair abnormality in monilethrix is a beading of the hair shaft caused by periodic narrowing with the nodes separated by about 0.7mm, and it is apparent that hHB1 and hHb6 are major hair cortex keratins.
New mutations in keratin 1 that cause bullous congenital ichthyosiform erythroderma and keratin 2e that cause ichthyosis bullosa of Siemens
TLDR
It is demonstrated that mutations in the KRT1 and KRT2E genes are deleterious to keratin filament network stability and lead to specific clinical inherited disorders of keratinization.
A mutation in the type II hair keratin KRT86 gene in a Han family with monilethrix☆
TLDR
There is a potential pathogenic gene in the subjects and the results expand the spectrum of mutations in the hHb6 gene, which may be pathogenic for monilethrix.
Mutations in the desmoglein 4 gene are associated with monilethrix-like congenital hypotrichosis.
TLDR
The observation that mutations in the DSG4 gene can cause monilethrix-like congenital hypotrichosis is presented and it is proposed that LAH and moniliform hair could overlap.
A Novel Missense Mutation, A118E, in the Helix Initiation Motif of the Type II Hair Cortex Keratin hHb6, Causing Monilethrix
TLDR
The pedigree of the family is shown andvirtually all affected individuals had hypotrichosis following shedding of initial hair and subsequently developed individually varying hair regrowth.
Recurrent E413K Mutation of hHb6 in a Japanese Family with Monilethrix
TLDR
A Japanese monilethrix family that has the most frequent mutation, the E413K mutation in hHb6, so far found in 26 families is described.
A study of phenotypic correlation with the genotypic status of HTM regions of KRTHB6 and KRTHB1 genes in monilethrix families of Indian origin.
TLDR
Interestingly, the two distinct phenotypes of: localized severe hair defect with beaded appearance confined to the scalp of all the affected members of Family 1 and of generalized unbeaded hair defect of moderate severity in Family 2, segregated in the two families, respectively, correlating with the two separate genotypes for the functionally critical HTM region of KRTHB1 gene in the background of E413K mutation.
De novo mutations in monilethrix
TLDR
Ten families with monilethrix in which the parents were not clinically affected are found, and the hair keratin hHB1, hHb3 and hB6 genes are sequenced in seven patients, finding no mutations or de novo germline missense mutations at the helix termination motif.
Autosomal-dominant woolly hair resulting from disruption of keratin 74 (KRT74), a potential determinant of human hair texture.
TLDR
The findings not only further underscore the crucial roles of the IRS-specific epithelial keratin genes Krt71-74 in hair disorders but also open the possibility that these genes might function as genetic determinants of normal variation in hair texture across mammalian species.
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References

SHOWING 1-10 OF 16 REFERENCES
A variable monilethrix phenotype associated with a novel mutation, Glu402Lys, in the helix termination motif of the type II hair keratin hHb1.
TLDR
A novel mutation in a French monilethrix family consists of a lysine substitution of another highly conserved glutamic acid residue, Glu402 (Glu106 of the 2B subdomain), in the EIATYRRLLEGEE motif of hHb1.
A mutational hotspot in the 2B domain of human hair basic keratin 6 (hHb6) in monilethrix patients.
TLDR
The results of sequencing this domain of human hair basic keratin 6 in 13 unrelated families or cases with monilethrix found the same mutation as previously found, a G to A transversion leading to a lysine for glutamic acid substitution in the 2B domain of hHb6.
A new mutation in the type II hair cortex keratin hHb1 involved in the inherited hair disorder monilethrix
TLDR
Two further unrelated monilethrix families are investigated as well as a single case, and a lysine substitution of the corresponding glutamic acid residue, Glu 403, in the type II hair keratin hHb1, is identified, suggesting that this site represents a mutational hotspot in these highly related type IIhair keratins.
Mutations in the hair cortex keratin hHb6 cause the inherited hair disease monilethrix
TLDR
These mutations provide the first direct evidence for involvement of hair keratins in hair disease.
A Splice Site Mutation in the Gene of the Human Type I Hair Keratin hHa1 Results in the Expression of a Tailless Keratin Isoform*
TLDR
The view of a noninvolvement of the keratin tail domain in filament assembly is confirmed and explains the lack of a pathological hair phenotype in hHa1-t positive individuals.
Human keratin diseases:
TLDR
The first mutations in a keratin‐associated protein, plectin, were shown to cause a variant of epidermolysis bullosa associated with late‐onset muscular dystrophy (MD‐EBS), and genetic linkage analysis suggests that the hair disorder monilethrix is likely to be due to a mutation in a hair keratin.
Linkage of monilethrix to the trichocyte and epithelial keratin gene cluster on 12q11-q13.
TLDR
A mutation in a trichocyte keratin gene is implicates in the pathogenesis of a structural hair disorder and a major group of structural hair proteins, the basic type II trichocytes keratins, map within this epithelial cytokeratin gene cluster.
A gene for monilethrix is closely linked to the type II keratin gene cluster at 12q13.
TLDR
This is the first mapping of a primary human hair disorder and the first evidence implicating a defect of the word 'hard' keratins of hair and nail disease.
Concurrence between the molecular overlap regions in keratin intermediate filaments and the locations of keratin mutations in genodermatoses.
TLDR
R residue positions 7-16 of the 1A and positions 107-117 of the 2B rod domain segments describe the extent of the molecular overlap window wherein mutations in keratin intermediate filaments are most likely to alter filament stability and lead to abnormalities.
Monilethrix: a keratin hHb6 mutation is co‐dominant with variable expression
TLDR
A large family with a E410D mutation in the evolutionary conserved helix termination motif of keratin hHb6 that was variably expressed among 12 heterozygousMembers, and severely expressed among 3 homozygous members is described.
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