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The Journal of Investigative Dermatology Jun 2006Monilethrix, an autosomal dominant human hair disorder, is caused by mutations in three type II hair cortex keratins. Rare cases of the disease with non-vertical...
Monilethrix, an autosomal dominant human hair disorder, is caused by mutations in three type II hair cortex keratins. Rare cases of the disease with non-vertical transmission have now been found to overlap with localized autosomal recessive hypotrichosis. The underlying gene, desmoglein 4 (DSG4), belongs to the desmosomal cadherin superfamily and is also expressed in the cortex of the hair follicle.
Topics: Animals; Desmogleins; Genes; Hair Diseases; Hair Follicle; Humans; Hypotrichosis; Mice; Mutation; Rats
PubMed: 16702971
DOI: 10.1038/sj.jid.5700266 -
International Journal of Trichology 2015Congenital hypotrichosis may be due to a number of causes and may have multiple systemic associations. A child born of second-degree consanguineous marriage was found to...
Congenital hypotrichosis may be due to a number of causes and may have multiple systemic associations. A child born of second-degree consanguineous marriage was found to have monilethrix as the cause of congenital hypotrichosis. A detailed systemic evaluation in the child revealed atrial septal defect and a hypoplastic right thumb leading to a diagnosis of coexisting Holt-Oram syndrome.
PubMed: 25878448
DOI: 10.4103/0974-7753.153455 -
The Journal of Investigative Dermatology Dec 1999Monilethrix is an autosomal dominant hair disorder characterized by a beaded appearance of the hair due to periodic thinning of the shaft. The phenotype shows variable...
Monilethrix is an autosomal dominant hair disorder characterized by a beaded appearance of the hair due to periodic thinning of the shaft. The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. Mutations of the helix-encoding region in two hair-specific keratins (hHb1 and hHb6) have been identified. We have now investigated two unrelated monilethrix patients and identified two different novel heterozygous point mutations of the same codon in exon 7 of the hHb6 gene. Dystrophic hair samples obtained from both patients showed the typical beaded appearance by scanning electron microscopy. Both mutations affected the first base of codon 402 (glutamic acid). In patient A, a G to C transition occurred causing a glutamine substitution (GAG to CAG: E402Q) whereas in patient B, the transition was G to A yielding a lysine substitution (GAG to AAG: E402K). The sequence of the 1A helical regions of hHb1 and hHb6 as well as the 2B helical region of hHb1, were normal. Unaffected relatives did not have the hHb6 mutation and this codon was found to be highly conserved showing no alteration in the normal population (100 alleles examined). Both mutations disrupted a Taq I restriction site and restriction fragment length polymorphism analysis showed that a diagnostic 361 bp fragment could confirm the mutation. Thus, two new point mutations of the hair-specific keratin gene hHb6 have been identified in this genetic disease.
Topics: Alopecia; Codon; Hair; Humans; Keratins; Mutation; Polymorphism, Restriction Fragment Length
PubMed: 10594761
DOI: 10.1046/j.1523-1747.1999.00777.x -
Differentiation; Research in Biological... Dec 2009The hair fiber is made of specialized keratinocytes, known as trichocytes, that primarily express hair keratins, which are cemented by a multitude of keratin-associated...
The hair fiber is made of specialized keratinocytes, known as trichocytes, that primarily express hair keratins, which are cemented by a multitude of keratin-associated proteins (KAPs). The hair keratins form the intermediate filament cytoskeleton of the trichocytes, which are linked to abundant cell-cell adhesion junctions, called desmosomes. Desmoglein 4 (DSG4) is the major desmosomal cadherin expressed in the hair shaft cortex where the hair keratins are highly expressed. In humans, mutations affecting either the hair keratins or DSG4 lead to beaded hair phenotypes with features of monilethrix. In this work, we postulated that the regulatory pathways governing the expression of hair shaft components, such as hair keratins and DSG4, are shared. Therefore, we studied the transcriptional regulation of DSG4 by transcription factors/pathways that are known regulators of hair keratin or KAP expression. We show that HOXC13, LEF1 and FOXN1 repress DSG4 transcription and provide in vitro and in vivo evidence correlating the Notch pathway with the activation and/or maintenance of DSG4 expression in the hair follicle.
Topics: Animals; Animals, Genetically Modified; Cell Differentiation; Desmogleins; Gene Expression Regulation; Hair; Humans; Mice; Mice, Knockout; Rats; Receptors, Notch; Signal Transduction; Transcription Factors; Transcription, Genetic
PubMed: 19683850
DOI: 10.1016/j.diff.2009.06.004 -
Journal of Clinical Pathology Dec 2005Microscopic examination of scalp hair can provide important diagnostic information in a range of paediatric conditions. It is a non-invasive and cost effective...
BACKGROUND
Microscopic examination of scalp hair can provide important diagnostic information in a range of paediatric conditions. It is a non-invasive and cost effective investigation, which is not widely performed.
AIMS
To examine retrospectively the value of hair examination by light microscopy, including polarising microscopy, in a specialist paediatric pathology department during a 15 year period (1989-2004) and to describe the morphological abnormalities indicative of specific paediatric conditions.
METHODS
Three hundred and twenty two hair samples were submitted. Microscopic changes were analysed in the light of clinical information categorised as: (1) erythroderma, (2) neurological impairment, (3) immunological/haematological defect, (4) ectodermal dysplasia, (5) abnormal hair only, and (6) non-specific/absent clinical details.
RESULTS
Abnormalities were evident in 49% of the samples. In 25%, the changes were compatible with specific diagnoses including Menkes disease, Netherton's syndrome, trichothiodystrophy, Griscelli and Chediak-Higashi syndromes, monilethrix, uncombable hair, and loose anagen syndromes. In respect of the clinical presentation groups noted above, diagnostic changes were seen in 41%, 32%, 33%, 0%, 29%, and 0%, respectively.
CONCLUSIONS
Morphological light microscopic examination of scalp hair is an inexpensive, rapid, and non-invasive investigation, which can provide valuable diagnostic information in a range of paediatric conditions.
Topics: Adolescent; Adult; Age Distribution; Child; Child, Preschool; Ectodermal Dysplasia; Hair; Hair Diseases; Humans; Ichthyosiform Erythroderma, Congenital; Infant; Infant, Newborn; Menkes Kinky Hair Syndrome; Mutation; Photomicrography; Retrospective Studies; Scalp; Syndrome
PubMed: 16311350
DOI: 10.1136/jcp.2005.027581 -
International Journal of Trichology 2017
PubMed: 28839397
DOI: 10.4103/ijt.ijt_72_16 -
The Journal of Investigative Dermatology Aug 1999Monilethrix, 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...
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.
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.
Topics: Amino Acid Sequence; Animals; Base Sequence; Female; Hair Diseases; Helix-Turn-Helix Motifs; Humans; Keratins; Male; Pedigree; Point Mutation
PubMed: 10469314
DOI: 10.1046/j.1523-1747.1999.00685.x -
Dermatology Practical & Conceptual Jan 2021
PubMed: 33354398
DOI: 10.5826/dpc.1101a80 -
The Journal of Investigative Dermatology Apr 1996Monilethrix is characterized by beaded or moniliform hair, which results from the periodic thinning of the hair shaft. The beaded hair thus produced is subject to excess...
Monilethrix is characterized by beaded or moniliform hair, which results from the periodic thinning of the hair shaft. The beaded hair thus produced is subject to excess weathering and premature fracturing at the internodes. Clinically, monilethrix presents with short, fragile, broken hair. The follicular abnormalities range from subtle perifollicular abnormalities range from subtle perifollicular erythema and hyperkeratosis to horny follicular papule formation. At the ultrastructural level, cytolysis and keratin tonofilament clumping (epidermolysis) are seen in the cortical cells of the bulb of the hair follicle. Microsatellite markers flanking the keratin gene clusters at 17q12-q21 and 12q11-q13 were used to perform linkage analysis in a monilethrix pedigree. This study demonstrates linkage of monilethrix in a pedigree to microsatellite DNA loci mapping to the region on chromosome 12 containing the type II keratin cluster. A major group of structural hair proteins, the basic type II trichocyte keratins, map within this epithelial cytokeratin gene cluster. This study implicates a mutation in a trichocyte keratin gene in the pathogenesis of a structural hair disorder.
Topics: Chromosomes, Human, Pair 12; Female; Genetic Linkage; Hair; Humans; Keratins; Male; Multigene Family; Mutation; Pedigree
PubMed: 8618025
DOI: 10.1111/1523-1747.ep12346400 -
The Journal of Investigative Dermatology Jun 2006Localized autosomal recessive hypotrichosis (LAH) is a recently defined disorder characterized by fragile, short, sparse hairs on the scalp, trunk, and extremities....
Localized autosomal recessive hypotrichosis (LAH) is a recently defined disorder characterized by fragile, short, sparse hairs on the scalp, trunk, and extremities. Mutations in desmoglein 4 (DSG4), a novel member of the desmosomal cadherin family that is expressed in the hair follicle as well as the suprabasal epidermis, have been found to underlie LAH. Thus far, the allelic series includes a recurrent intragenic deletion identified in affected Pakastani kindreds and a missense mutation detected in an Iraqi family. We report three siblings of Iraqi and Iranian origin with LAH that presented with congenital scalp erosions and monilethrix-like hairs, features that have not been previously described in this disorder. Follicular hyperkeratotic papules and marked pruritus were also prominent clinical findings. Novel compound heterozygous DSG4 mutations, including a splice-site mutation and a missense mutation that disrupts a conserved calcium-binding site in the extracellular (EC)2-EC3 interface, were found to underlie the disease in this family. These observations broaden the phenotypic and genotypic spectrum of LAH, further illustrating the consequences of DSG4 dysfunction on epidermal and hair shaft integrity.
Topics: Amino Acid Sequence; Child, Preschool; DNA Mutational Analysis; Desmogleins; Female; Hair; Hair Diseases; Humans; Hypotrichosis; Infant, Newborn; Male; Molecular Sequence Data; Protein Conformation; Scalp; Scalp Dermatoses
PubMed: 16543896
DOI: 10.1038/sj.jid.5700237