The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
Jürgen Schweizer - One of the best experts on this subject based on the ideXlab platform.
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Hair follicle-specific keratins and their diseases
Experimental Cell Research, 2007Co-Authors: Jürgen Schweizer, Lutz Langbein, Michael A. Rogers, Hermelita WinterAbstract:Abstract The human keratin family comprises 54 members, 28 type I and 26 type II. Out of the 28 type I keratins, 17 are epithelial and 11 are hair keratins. Similarly, the 26 type II members comprise 20 epithelial and 6 hair keratins. As, however, 9 out of the 37 epithelial keratins are specifically expressed in the hair follicle, the total number of hair follicle-specific keratins (26) almost equals that of those expressed in the various forms of epithelia (28). Up to now, more than half of the latter have been found to be involved in inherited diseases, with mutated type I and type II members being roughly equally causal. In contrast, out of the 26 hair follicle-specific keratins only 5 have, at present, been associated with inherited hair disorders, while one keratin merely acts as a risk factor. In addition, all hair follicle-specific keratins involved in pathologies are type II keratins. Here we provide a detailed description of the respective hair diseases which are either due to mutations in hair keratins (Monilethrix, ectodermal dysplasia of hair and nail type) or hair follicle-specific epithelial keratins (two mouse models, RCO3 and Ca Rin as well as pseudofolliculitis barbae).
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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
Journal of Investigative Dermatology, 1999Co-Authors: Hermelita Winter, Michael A. Rogers, Robin D Clark, Caspar Tarraswahlberg, Jürgen SchweizerAbstract: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 hHb1 Glu402Lys, have been reported in a distinctly lower number of cases. In this study, we describe the equivalent of the hHb1 Glu402Lys mutation in the HTM of cortex keratin hHb6. The mutation occurred in an American family in which it could only be detected in one clinically affected individual. Thus the underlying G→A transition represents a spontaneous germ-line mutation in the hHb6 gene. This new mutation indicates that both the hHb6/hHb1 Glu413Lys substitution and the hHb6/hHb1 Glu402Lys substitution, represent mutational hotspots in the HTM of type II cortex keratins. However, we also describe a Monilethrix-causing mutation in the helix initiation motif, HIM, of the cortex keratin hHb6. The critical Asn114Asp substitution was only found in affected members of a large Swedish three-generation family. Considering that since childhood, half of the affected individuals suffer from complete baldness and follicular keratosis, the new HIM mutation seems to be associated with a rather severe disease phenotype. In conclusion, our data strongly suggest that Monilethrix is a disease of the hair cortex, whose etiology is interesting in that causative mutations seem to be restricted to type II hair keratins.
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a variable Monilethrix phenotype associated with a novel mutation glu402lys in the helix termination motif of the type ii hair keratin hhb1
Journal of Investigative Dermatology, 1998Co-Authors: Hermelita Winter, Michael A. Rogers, Christine Labreze, Valerie Chapalain, Jean Etienne Surlevebazeille, Michel Mercier, Alain Taieb, Jürgen SchweizerAbstract:Monilethrix is a rare human hair disorder with autosomal dominant transmission that can be caused by mutations in hair keratins. Up until now, pathogenic mutations in the type II hair cortex keratins hHb6 and hHb1 were restricted to a highly conserved glutamic acid residue Glu413 (Glu117 of the 2B subdomains) in the EIATYRRLLEGEE helix termination motif of the two keratins. The critical glutamic acid residue was substituted either by a lysine or, less frequently, by an aspartic acid residue. Here we report a novel mutation in a French Monilethrix family, which again consists of a lysine substitution of another highly conserved glutamic acid residue, Glu402 (Glu106 of the 2B subdomain), in the EIATYRRLLEGEE motif of hHb1. Family members bearing the hHb1 Glu402Lys mutation exhibit a particularly variable disease phenotype. The pedigree comprises two infant members, one with pronounced dystrophic alopecia, follicular keratosis, and clear-cut moniliform hair, and one with no hair loss at all and moniliform hair detectable only by electron microscopy, as well as an adult individual without any clinically or electron microscopically detectable symptoms, but with clear historical proof of the disease.
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a new mutation in the type ii hair cortex keratin hhb1 involved in the inherited hair disorder Monilethrix
Human Genetics, 1997Co-Authors: Hermelita Winter, Michael A. Rogers, Howard P. Stevens, Mathias Gebhardt, Uwe Wollina, Lionell Boxall, David Chitayat, Riyana Babulhirji, Abreham Zlotogorski, Jürgen SchweizerAbstract:Monilethrix is a rare dominant hair disease characterized by beaded or moniliform hair which results from the periodic thinning of the hair shaft and shows a high propensity to excess weathering and fracturing. Several cases of Monilethrix have been linked to the type II keratin gene cluster on chromosome 12q13 and causative heterozygous mutations of a highly conserved glutamic acid residue (Glu 410 Lys and Glu 410 Asp) in the helix termination motif of the type II hair keratin hHb6 have recently been identified in Monilethrix patients of two unrelated families. In the present study, we have investigated two further unrelated Monilethrix families as well as a single case. Affected members of one family and the single patient exhibited the prevalent hHb6 Glu 410 Lys mutation. In the second family, we identified in affected individuals a lysine substitution of the corresponding glutamic acid residue, Glu 403, in the type II hair keratin hHb1, suggesting that this site represents a mutational hotspot in these highly related type II hair keratins. Both hHb1 and hHb6 are largely coexpressed in cortical trichocytes of the hair shaft. This indicates that Monilethrix is a disease of the hair cortex.
Hermelita Winter - One of the best experts on this subject based on the ideXlab platform.
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Hair follicle-specific keratins and their diseases
Experimental Cell Research, 2007Co-Authors: Jürgen Schweizer, Lutz Langbein, Michael A. Rogers, Hermelita WinterAbstract:Abstract The human keratin family comprises 54 members, 28 type I and 26 type II. Out of the 28 type I keratins, 17 are epithelial and 11 are hair keratins. Similarly, the 26 type II members comprise 20 epithelial and 6 hair keratins. As, however, 9 out of the 37 epithelial keratins are specifically expressed in the hair follicle, the total number of hair follicle-specific keratins (26) almost equals that of those expressed in the various forms of epithelia (28). Up to now, more than half of the latter have been found to be involved in inherited diseases, with mutated type I and type II members being roughly equally causal. In contrast, out of the 26 hair follicle-specific keratins only 5 have, at present, been associated with inherited hair disorders, while one keratin merely acts as a risk factor. In addition, all hair follicle-specific keratins involved in pathologies are type II keratins. Here we provide a detailed description of the respective hair diseases which are either due to mutations in hair keratins (Monilethrix, ectodermal dysplasia of hair and nail type) or hair follicle-specific epithelial keratins (two mouse models, RCO3 and Ca Rin as well as pseudofolliculitis barbae).
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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
Journal of Investigative Dermatology, 1999Co-Authors: Hermelita Winter, Michael A. Rogers, Robin D Clark, Caspar Tarraswahlberg, Jürgen SchweizerAbstract: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 hHb1 Glu402Lys, have been reported in a distinctly lower number of cases. In this study, we describe the equivalent of the hHb1 Glu402Lys mutation in the HTM of cortex keratin hHb6. The mutation occurred in an American family in which it could only be detected in one clinically affected individual. Thus the underlying G→A transition represents a spontaneous germ-line mutation in the hHb6 gene. This new mutation indicates that both the hHb6/hHb1 Glu413Lys substitution and the hHb6/hHb1 Glu402Lys substitution, represent mutational hotspots in the HTM of type II cortex keratins. However, we also describe a Monilethrix-causing mutation in the helix initiation motif, HIM, of the cortex keratin hHb6. The critical Asn114Asp substitution was only found in affected members of a large Swedish three-generation family. Considering that since childhood, half of the affected individuals suffer from complete baldness and follicular keratosis, the new HIM mutation seems to be associated with a rather severe disease phenotype. In conclusion, our data strongly suggest that Monilethrix is a disease of the hair cortex, whose etiology is interesting in that causative mutations seem to be restricted to type II hair keratins.
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a variable Monilethrix phenotype associated with a novel mutation glu402lys in the helix termination motif of the type ii hair keratin hhb1
Journal of Investigative Dermatology, 1998Co-Authors: Hermelita Winter, Michael A. Rogers, Christine Labreze, Valerie Chapalain, Jean Etienne Surlevebazeille, Michel Mercier, Alain Taieb, Jürgen SchweizerAbstract:Monilethrix is a rare human hair disorder with autosomal dominant transmission that can be caused by mutations in hair keratins. Up until now, pathogenic mutations in the type II hair cortex keratins hHb6 and hHb1 were restricted to a highly conserved glutamic acid residue Glu413 (Glu117 of the 2B subdomains) in the EIATYRRLLEGEE helix termination motif of the two keratins. The critical glutamic acid residue was substituted either by a lysine or, less frequently, by an aspartic acid residue. Here we report a novel mutation in a French Monilethrix family, which again consists of a lysine substitution of another highly conserved glutamic acid residue, Glu402 (Glu106 of the 2B subdomain), in the EIATYRRLLEGEE motif of hHb1. Family members bearing the hHb1 Glu402Lys mutation exhibit a particularly variable disease phenotype. The pedigree comprises two infant members, one with pronounced dystrophic alopecia, follicular keratosis, and clear-cut moniliform hair, and one with no hair loss at all and moniliform hair detectable only by electron microscopy, as well as an adult individual without any clinically or electron microscopically detectable symptoms, but with clear historical proof of the disease.
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a new mutation in the type ii hair cortex keratin hhb1 involved in the inherited hair disorder Monilethrix
Human Genetics, 1997Co-Authors: Hermelita Winter, Michael A. Rogers, Howard P. Stevens, Mathias Gebhardt, Uwe Wollina, Lionell Boxall, David Chitayat, Riyana Babulhirji, Abreham Zlotogorski, Jürgen SchweizerAbstract:Monilethrix is a rare dominant hair disease characterized by beaded or moniliform hair which results from the periodic thinning of the hair shaft and shows a high propensity to excess weathering and fracturing. Several cases of Monilethrix have been linked to the type II keratin gene cluster on chromosome 12q13 and causative heterozygous mutations of a highly conserved glutamic acid residue (Glu 410 Lys and Glu 410 Asp) in the helix termination motif of the type II hair keratin hHb6 have recently been identified in Monilethrix patients of two unrelated families. In the present study, we have investigated two further unrelated Monilethrix families as well as a single case. Affected members of one family and the single patient exhibited the prevalent hHb6 Glu 410 Lys mutation. In the second family, we identified in affected individuals a lysine substitution of the corresponding glutamic acid residue, Glu 403, in the type II hair keratin hHb1, suggesting that this site represents a mutational hotspot in these highly related type II hair keratins. Both hHb1 and hHb6 are largely coexpressed in cortical trichocytes of the hair shaft. This indicates that Monilethrix is a disease of the hair cortex.
Michael A. Rogers - One of the best experts on this subject based on the ideXlab platform.
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Hair follicle-specific keratins and their diseases
Experimental Cell Research, 2007Co-Authors: Jürgen Schweizer, Lutz Langbein, Michael A. Rogers, Hermelita WinterAbstract:Abstract The human keratin family comprises 54 members, 28 type I and 26 type II. Out of the 28 type I keratins, 17 are epithelial and 11 are hair keratins. Similarly, the 26 type II members comprise 20 epithelial and 6 hair keratins. As, however, 9 out of the 37 epithelial keratins are specifically expressed in the hair follicle, the total number of hair follicle-specific keratins (26) almost equals that of those expressed in the various forms of epithelia (28). Up to now, more than half of the latter have been found to be involved in inherited diseases, with mutated type I and type II members being roughly equally causal. In contrast, out of the 26 hair follicle-specific keratins only 5 have, at present, been associated with inherited hair disorders, while one keratin merely acts as a risk factor. In addition, all hair follicle-specific keratins involved in pathologies are type II keratins. Here we provide a detailed description of the respective hair diseases which are either due to mutations in hair keratins (Monilethrix, ectodermal dysplasia of hair and nail type) or hair follicle-specific epithelial keratins (two mouse models, RCO3 and Ca Rin as well as pseudofolliculitis barbae).
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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
Journal of Investigative Dermatology, 1999Co-Authors: Hermelita Winter, Michael A. Rogers, Robin D Clark, Caspar Tarraswahlberg, Jürgen SchweizerAbstract: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 hHb1 Glu402Lys, have been reported in a distinctly lower number of cases. In this study, we describe the equivalent of the hHb1 Glu402Lys mutation in the HTM of cortex keratin hHb6. The mutation occurred in an American family in which it could only be detected in one clinically affected individual. Thus the underlying G→A transition represents a spontaneous germ-line mutation in the hHb6 gene. This new mutation indicates that both the hHb6/hHb1 Glu413Lys substitution and the hHb6/hHb1 Glu402Lys substitution, represent mutational hotspots in the HTM of type II cortex keratins. However, we also describe a Monilethrix-causing mutation in the helix initiation motif, HIM, of the cortex keratin hHb6. The critical Asn114Asp substitution was only found in affected members of a large Swedish three-generation family. Considering that since childhood, half of the affected individuals suffer from complete baldness and follicular keratosis, the new HIM mutation seems to be associated with a rather severe disease phenotype. In conclusion, our data strongly suggest that Monilethrix is a disease of the hair cortex, whose etiology is interesting in that causative mutations seem to be restricted to type II hair keratins.
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a variable Monilethrix phenotype associated with a novel mutation glu402lys in the helix termination motif of the type ii hair keratin hhb1
Journal of Investigative Dermatology, 1998Co-Authors: Hermelita Winter, Michael A. Rogers, Christine Labreze, Valerie Chapalain, Jean Etienne Surlevebazeille, Michel Mercier, Alain Taieb, Jürgen SchweizerAbstract:Monilethrix is a rare human hair disorder with autosomal dominant transmission that can be caused by mutations in hair keratins. Up until now, pathogenic mutations in the type II hair cortex keratins hHb6 and hHb1 were restricted to a highly conserved glutamic acid residue Glu413 (Glu117 of the 2B subdomains) in the EIATYRRLLEGEE helix termination motif of the two keratins. The critical glutamic acid residue was substituted either by a lysine or, less frequently, by an aspartic acid residue. Here we report a novel mutation in a French Monilethrix family, which again consists of a lysine substitution of another highly conserved glutamic acid residue, Glu402 (Glu106 of the 2B subdomain), in the EIATYRRLLEGEE motif of hHb1. Family members bearing the hHb1 Glu402Lys mutation exhibit a particularly variable disease phenotype. The pedigree comprises two infant members, one with pronounced dystrophic alopecia, follicular keratosis, and clear-cut moniliform hair, and one with no hair loss at all and moniliform hair detectable only by electron microscopy, as well as an adult individual without any clinically or electron microscopically detectable symptoms, but with clear historical proof of the disease.
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a new mutation in the type ii hair cortex keratin hhb1 involved in the inherited hair disorder Monilethrix
Human Genetics, 1997Co-Authors: Hermelita Winter, Michael A. Rogers, Howard P. Stevens, Mathias Gebhardt, Uwe Wollina, Lionell Boxall, David Chitayat, Riyana Babulhirji, Abreham Zlotogorski, Jürgen SchweizerAbstract:Monilethrix is a rare dominant hair disease characterized by beaded or moniliform hair which results from the periodic thinning of the hair shaft and shows a high propensity to excess weathering and fracturing. Several cases of Monilethrix have been linked to the type II keratin gene cluster on chromosome 12q13 and causative heterozygous mutations of a highly conserved glutamic acid residue (Glu 410 Lys and Glu 410 Asp) in the helix termination motif of the type II hair keratin hHb6 have recently been identified in Monilethrix patients of two unrelated families. In the present study, we have investigated two further unrelated Monilethrix families as well as a single case. Affected members of one family and the single patient exhibited the prevalent hHb6 Glu 410 Lys mutation. In the second family, we identified in affected individuals a lysine substitution of the corresponding glutamic acid residue, Glu 403, in the type II hair keratin hHb1, suggesting that this site represents a mutational hotspot in these highly related type II hair keratins. Both hHb1 and hHb6 are largely coexpressed in cortical trichocytes of the hair shaft. This indicates that Monilethrix is a disease of the hair cortex.
Jonathan L. Rees - One of the best experts on this subject based on the ideXlab platform.
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identification of novel mutations in basic hair keratins hhb1 and hhb6 in Monilethrix implications for protein structure and clinical phenotype
Journal of Investigative Dermatology, 1999Co-Authors: Bernhard P Korge, Jonathan L. Rees, Heiko Traupe, Mark A Birchmachin, Henning Hamm, Catherine S Jury, Alan D Irvine, E Healy, A G Messenger, Susan HolmesAbstract:Monilethrix is an hereditary hair dystrophy recently shown to be due to mutations in the helix termination motif of two type II (basic) human hair keratin genes, hHb1 and hHb6. It has been suggested that mutation in hHb1 produces a less severe phenotype. We have studied hair keratin genes and clinical features in 18 unrelated pedigrees of Monilethrix from Germany, Scotland, Northern Ireland, and Portugal, in 13 of which mutations have not previously been identified. By examining the rod domains of hHb1, hHb3 and hHb6, we have identified mutations in nine of the new pedigrees. We again found the glutamine-lysine substitution (E413K) in the helix termination motif of hHb6 in two families, and in another, the corresponding E413K substitution in the hHb1 gene. In four families a similar substitution E402K was present in a nearby residue. In addition two novel mutations within the helix initiation motif of hHb6 were found in Scottish and Portuguese cases, in whom the same highly conserved asparagine residue N114 was mutated to histidine (N114H) or aspartic acid (N114D) residues, respectively. In four other Monilethrix pedigrees mutations in these domains of hHb1, hHb3, and hHb6 were not found. The mutations identified predict a variety of possible structural consequences for the keratin molecule. A comparison of clinical features and severity between cases with hHb1 and hHb6 mutations does not suggest distinct effects on phenotype, with the possible exception of nail dystrophy, commoner with hHb1 defects. Other factors are required to explain the marked variation in clinical severity within and between cases.
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Mapping of Monilethrix to the type II keratin gene cluster at chromosome 12q13 in three new families, including one with variable expressivity.
British Journal of Dermatology, 1997Co-Authors: Mark A. Birch-machin, Eugene Healy, Faye Haldane, C.e. Belgaid, S. Darlington, A.m. Stephenson, Colin S. Munro, Andrew G. Messenger, Richard Turner, Jonathan L. ReesAbstract:Monilethrix is an autosomal dominant disorder chiefly affecting hair. The degree of hair dystrophy is highly variable, as is the presence of additional features, such as follicular keratoses. In three British families of Monilethrix, linkage has recently been reported to the type II keratin gene cluster at chromosome 12q13, and it has been suggested that the disease is due to a defect in the hard keratins of hair and nail. If Monilethrix is a keratin disorder, we would predict that some pedigrees might map to the type I keratin gene cluster on 17q where hard keratin genes are also found. We have now studied clinically and by linkage analysis three new and unrelated pedigrees from England, Scotland and Spain, the first of which showed a variant phenotype. In this family the disease was expressed in four of 12 cases only as a follicular keratosis of the neck, elbows and knees, and without clinical or historical evidence of hair anomalies: non-penetrance in an obligate carrier was also observed. In all three families, we have established linkage to a series of microsatellite markers at the type II locus at 12q13 (Zmax=6.34 at 0=0.00 for D12S368) and have excluded linkage from the type I keratin gene cluster on 17q. It remains probable that Monilethrix is a disorder of hard keratins, but at present there is no evidence that it is due to defects in type I keratins.
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mapping of Monilethrix to the type ii keratin gene cluster at chromosome 12q13 in three new families including one with variable expressivity
British Journal of Dermatology, 1997Co-Authors: Mark A Birchmachin, Eugene Healy, Faye Haldane, C.e. Belgaid, S. Darlington, A.m. Stephenson, Colin S. Munro, Andrew G. Messenger, Richard Turner, Jonathan L. ReesAbstract:Monilethrix is an autosomal dominant disorder chiefly affecting hair. The degree of hair dystrophy is highly variable, as is the presence of additional features, such as follicular keratoses. In three British families of Monilethrix, linkage has recently been reported to the type II keratin gene cluster at chromosome 12q13, and it has been suggested that the disease is due to a defect in the hard keratins of hair and nail. If Monilethrix is a keratin disorder, we would predict that some pedigrees might map to the type I keratin gene cluster on 17q where hard keratin genes are also found. We have now studied clinically and by linkage analysis three new and unrelated pedigrees from England, Scotland and Spain, the first of which showed a variant phenotype. In this family the disease was expressed in four of 12 cases only as a follicular-keratosis of the neck, elbows and knees, and without clinical or historical evidence of hair anomalies; non-penetrance in an obligate carrier was also observed. In all three families, we have established linkage to a series of microsatellite markers at the type II locus at 12q13 (Zmax = 6.34 at theta = 0.00 for D12S368) and have excluded linkage from the type I keratin gene cluster on 17q. It remains probable that Monilethrix is a disorder of hard keratins, but at present there is no evidence that it is due to defects in type I keratins.
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A gene for Monilethrix is closely linked to the type II keratin gene cluster at 12q13
Human Molecular Genetics, 1995Co-Authors: Eugene Healy, C.e. Belgaid, Jonathan L. Rees, Susan Holmes, Anthea Stephenson, W.h. Irwin Mclean, Colin S. MunroAbstract:Monilethrix is an uncommon hereditary disorder of hair and nail which produces hair fragility and a variable alopecia. Many of the dystrophic hairs have a unique beaded morphology. Ultrastructural changes suggest a defect in the microfilament structure of the cortex of the hair shaft,and hence the cysteine-rich trichocyte keratins are candidate genes. Here, in two families with autosomal dominant Monilethrix, we have excluded linkage to the type I keratin gene cluster on chromosome 17q, but show that the disorder is closely linked to the type II keratin cluster on 12q, where genes for basic trichocyte keratins are found. The combined maximum lod score for D12S96 was 12.27 at theta=0.0. 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.
Colin S. Munro - One of the best experts on this subject based on the ideXlab platform.
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Mapping of Monilethrix to the type II keratin gene cluster at chromosome 12q13 in three new families, including one with variable expressivity.
British Journal of Dermatology, 1997Co-Authors: Mark A. Birch-machin, Eugene Healy, Faye Haldane, C.e. Belgaid, S. Darlington, A.m. Stephenson, Colin S. Munro, Andrew G. Messenger, Richard Turner, Jonathan L. ReesAbstract:Monilethrix is an autosomal dominant disorder chiefly affecting hair. The degree of hair dystrophy is highly variable, as is the presence of additional features, such as follicular keratoses. In three British families of Monilethrix, linkage has recently been reported to the type II keratin gene cluster at chromosome 12q13, and it has been suggested that the disease is due to a defect in the hard keratins of hair and nail. If Monilethrix is a keratin disorder, we would predict that some pedigrees might map to the type I keratin gene cluster on 17q where hard keratin genes are also found. We have now studied clinically and by linkage analysis three new and unrelated pedigrees from England, Scotland and Spain, the first of which showed a variant phenotype. In this family the disease was expressed in four of 12 cases only as a follicular keratosis of the neck, elbows and knees, and without clinical or historical evidence of hair anomalies: non-penetrance in an obligate carrier was also observed. In all three families, we have established linkage to a series of microsatellite markers at the type II locus at 12q13 (Zmax=6.34 at 0=0.00 for D12S368) and have excluded linkage from the type I keratin gene cluster on 17q. It remains probable that Monilethrix is a disorder of hard keratins, but at present there is no evidence that it is due to defects in type I keratins.
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mapping of Monilethrix to the type ii keratin gene cluster at chromosome 12q13 in three new families including one with variable expressivity
British Journal of Dermatology, 1997Co-Authors: Mark A Birchmachin, Eugene Healy, Faye Haldane, C.e. Belgaid, S. Darlington, A.m. Stephenson, Colin S. Munro, Andrew G. Messenger, Richard Turner, Jonathan L. ReesAbstract:Monilethrix is an autosomal dominant disorder chiefly affecting hair. The degree of hair dystrophy is highly variable, as is the presence of additional features, such as follicular keratoses. In three British families of Monilethrix, linkage has recently been reported to the type II keratin gene cluster at chromosome 12q13, and it has been suggested that the disease is due to a defect in the hard keratins of hair and nail. If Monilethrix is a keratin disorder, we would predict that some pedigrees might map to the type I keratin gene cluster on 17q where hard keratin genes are also found. We have now studied clinically and by linkage analysis three new and unrelated pedigrees from England, Scotland and Spain, the first of which showed a variant phenotype. In this family the disease was expressed in four of 12 cases only as a follicular-keratosis of the neck, elbows and knees, and without clinical or historical evidence of hair anomalies; non-penetrance in an obligate carrier was also observed. In all three families, we have established linkage to a series of microsatellite markers at the type II locus at 12q13 (Zmax = 6.34 at theta = 0.00 for D12S368) and have excluded linkage from the type I keratin gene cluster on 17q. It remains probable that Monilethrix is a disorder of hard keratins, but at present there is no evidence that it is due to defects in type I keratins.
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A gene for Monilethrix is closely linked to the type II keratin gene cluster at 12q13
Human Molecular Genetics, 1995Co-Authors: Eugene Healy, C.e. Belgaid, Jonathan L. Rees, Susan Holmes, Anthea Stephenson, W.h. Irwin Mclean, Colin S. MunroAbstract:Monilethrix is an uncommon hereditary disorder of hair and nail which produces hair fragility and a variable alopecia. Many of the dystrophic hairs have a unique beaded morphology. Ultrastructural changes suggest a defect in the microfilament structure of the cortex of the hair shaft,and hence the cysteine-rich trichocyte keratins are candidate genes. Here, in two families with autosomal dominant Monilethrix, we have excluded linkage to the type I keratin gene cluster on chromosome 17q, but show that the disorder is closely linked to the type II keratin cluster on 12q, where genes for basic trichocyte keratins are found. The combined maximum lod score for D12S96 was 12.27 at theta=0.0. 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.