1/43. A mutation detection strategy for the human keratin 6A gene and novel missense mutations in two cases of pachyonychia congenita type 1.pachyonychia congenita type 1 (PC-1) is an autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy, focal non-epidermolytic palmoplantar keratoderma and variable features of oral leukokeratosis and follicular keratosis. Previously, we have shown that this disease can be caused by mutations in type I keratin K16 and one mutation has been reported in its type II keratin expression partner, K6a. mutation analysis for K6a has been hampered by the presence of multiple copies of the K6 gene in the human genome, of which some are expressed and others are pseudogenes. Here, we describe a mutation detection strategy where the entire KRT6A gene, approximately 7 kb, is specifically amplified by long-range PCR. Using this technique, we have detected two novel mutations in the 1A domain of the K6a polypeptide, N171K and F174S. Mutations were confirmed in the affected individuals and were excluded from 50 unaffected unrelated individuals by restriction enzyme analysis of KRT6A PCR products. Additionally, mutation N171K was confirmed by RT-PCR in mRNA derived from lesional palmoplantar epidermis of an affected individual, confirming the specificity of the genomic PCR for the functional K6a gene. This, together with a similar strategy which we have developed for the K16 gene, provide a robust system for mutation detection and prenatal diagnosis for patients with PC-1.- - - - - - - - - - ranking = 1keywords = palm (Clic here for more details about this article) |
2/43. Identification of sporadic mutations in the helix initiation motif of keratin 6 in two pachyonychia congenita patients: further evidence for a mutational hot spot.pachyonychia congenita (PC) is a rare, autosomal dominant, ectodermal dysplasia characterized most distinctly by the presence of symmetric nail hypertrophy. In the Jadassohn-Lewandowsky form, or PC-1, additional cutaneous manifestations may include palmoplantar hyperkeratosis, hyperhidrosis, follicular keratoses, and oral leukokeratosis. Mutations have previously been identified in the 1A helix initiation motif of either keratin 6 or keratin 16 in patients with PC-1. In the current study, we have identified 2 sporadic, heterozygous mutations in the 1A helix region of the K6 isoform (K6a). The first mutation identified was a 3 base pair deletion (K6adelta N171). The second mutation was a C-to-A transversion resulting in an amino acid substitution (K6a N171K). These data, in combination with previous reports, provide further evidence that this location is a mutational hot spot.- - - - - - - - - - ranking = 0.5keywords = palm (Clic here for more details about this article) |
3/43. Cloning of multiple keratin 16 genes facilitates prenatal diagnosis of pachyonychia congenita type 1.pachyonychia congenita type 1 (PC-1) is an autosomal dominant ectodermal dysplasia characterized by severe nail dystrophy, focal non-epidermolytic palmoplantar keratoderma (FNEPPK) and oral lesions. We have previously shown that mutations in keratin K16 cause fragility of specific epithelia resulting in phenotypes of PC-1 or FNEPPK alone. These earlier analyses employed an RT-PCR approach to avoid amplification of K16-like pseudogenes. Here, we have cloned the K16 gene (KRT16A) and two homologous pseudogenes (psiKRT16B and psiKRT16C), allowing development of a genomic mutation detection strategy based on a long-range PCR, which is specific for the functional K16 gene. We report a novel heterozygous 3 bp deletion mutation (388del3) in K16 in a sporadic case of PC-1. The mutation was detected in genomic dna and confirmed at the mRNA level by RT-PCR, showing that our genomic PCR system is reliable for K16 mutation detection. Using this system, we carried out the first prenatal diagnosis for PC-1 using CVS material, correctly predicting a normal fetus. This work will greatly improve K16 mutation analysis and allow predictive testing for PC-1 and the related phenotype of FNEPPK.- - - - - - - - - - ranking = 0.5keywords = palm (Clic here for more details about this article) |
4/43. Novel proline substitution mutations in keratin 16 in two cases of pachyonychia congenita type 1.pachyonychia congenita (PC) is a group of inherited ectodermal dysplasias, the characteristic phenotype being hypertrophic nail dystrophy. Two main clinical subtypes, PC-1 and PC-2, are inherited as autosomal dominant disorders, but other less well characterized clinical forms also exist. The PC-1 phenotype may be distinguished by the absence of the epidermal cysts found in PC-2, and it has been shown to be caused by mutations in either keratin K16 or its expression partner, the K6a isoform of K6. Mutations in K16 have also been shown to cause a milder related phenotype, focal non-epidermolytic palmoplantar keratoderma. Recently, we have developed a long-range polymerase chain reaction (PCR) strategy which allows specific amplification of the entire functional K16 gene (KRT16A), without amplification of the two K16 pseudogenes (psiKRT16B and psiKRT16C), enabling mutation analysis based on genomic dna. Here, using this methodology, we describe novel mutations R127P and Q122P in the helix 1A domain of K16 in two families presenting with PC-1. Both mutations were excluded from 50 normal unrelated individuals by restriction enzyme analysis of K16 PCR fragments. In one family, ultrastructural analysis was performed, revealing distinctive tonofilament abnormalities. Specifically, keratin filament bundles were greatly condensed, but did not form the dense amorphous aggregates seen in a number of other keratin disorders. In the second kindred, autosomal dominant cataract was present in some but not all members affected by PC. As the cataract phenotype did not fully cosegregate with the K16 mutation, and given that K16 is not expressed in the lens, these two phenotypes may be coincidental.- - - - - - - - - - ranking = 0.5keywords = palm (Clic here for more details about this article) |
5/43. Nail matrix arrest following hand-foot-mouth disease: a report of five children.hand-foot-mouth disease (HFMD) is a contagious enteroviral infection occurring primarily in children and characterized by a vesicular palmoplantar eruption and erosive stomatitis. Nail matrix arrest has been associated with a variety of drug exposures and systemic illnesses, including infections, and may result in a variety of changes, including transverse ridging (Beau's lines) and nail shedding (onychomadesis). The association of HFMD with Beau's lines and onychomadesis has not been reported previously. Five children, ages 22 months-4 years, presented with Beau's lines and/or onychomadesis following physician-diagnosed HFMD by 3-8 weeks. Three of the five patients experienced fever with HFMD, and none had a history of nail trauma, periungual dermatitis, periungual vesicular lesions, or a significant medication intake history. All patients experienced HFMD within 4 weeks of one another, and all resided in the suburbs of the chicago metropolitan area. In all patients the nail changes were temporary with spontaneous normal regrowth. The mechanism of the nail matrix arrest is unclear, but the timing and geographic clustering of the patients suggests an epidemic caused by the same viral strain.- - - - - - - - - - ranking = 0.5keywords = palm (Clic here for more details about this article) |
6/43. Similarities between a conjoined nail and the palmar nail syndrome.The congenital palmar nail syndrome consists of a triad of palmar nail, absent finger flexion and abnormalities of the distal phalanx. There are two main theories about the pathogenesis of this syndrome: the ancestral reversion theory and the duplication theory. In this paper, similarities between a conjoined nail in conjoined twins and the palmar nail syndrome are described to support the duplication theory.- - - - - - - - - - ranking = 3.5keywords = palm (Clic here for more details about this article) |
7/43. Peculiar facial appearance and generalized brachydactyly in a patient with congenital onychodysplasia of the index fingers (Iso-Kikuchi syndrome).We report on a patient with clinical manifestations consistent with a diagnosis of congenital onychodysplasia of the index fingers (COIF). This syndrome has been found mainly in japan, and as far as we know, this is the first case reported in italy. In addition to the typical bilateral split nail of the second finger, the patient showed bilateral inguinal hernia, a peculiar face, and short hands. The metacarpophalangeal profile showed a generalized brachydactyly with all the hand long bones below x3 SD. The patient's father showed a peculiar kind of micronychia on both the fifth toes, suggesting a possible autosomal dominant transmission of the syndrome. In utero ischemia of the palmar digital artery and a dysplastic change in the crescent-shaped cap of the distal phalanx are the two main candidate pathogenetic mechanisms that have been proposed. In our opinion, the gradual broadening of the spectrum of this syndrome brings support to the hypothesis of a basal dysplastic pathogenetic mechanism involving not only the index fingers but also perhaps other tissues outside. We think that for the moment the definition of COIF for this syndrome should be maintained, the alternative proposed term "congenital onychodysplasia" being too indefinite.- - - - - - - - - - ranking = 0.5keywords = palm (Clic here for more details about this article) |
8/43. Knuckle pads, leukonychia, deafness, and keratosis palmoplantaris: report of a family.A family is described in which knuckle pads, leukonychia, deafness, and keratosis palmoplantaris are present as a syndrome is several members. This is the second such family reported demonstrating that keratosis palmoplantaris is part of the syndrome. Inheritance pattern is probably autosomal dominant.- - - - - - - - - - ranking = 3keywords = palm (Clic here for more details about this article) |
9/43. An acantholytic dyskeratotic epidermal naevus with other features of Darier's disease on the same side of the body.Many epidermal naevi with the histology of Darier's disease have been reported. In the absence of associated features of Darier's disease, they cannot be assumed to have a common pathogenesis with it, and it has been suggested that they are better classified as acantholytic dyskeratotic epidermal naevi rather than naevoid Darier's disease. We describe a patient with such a naevus who had typical nail and palmar changes of Darier's disease on the same side of the body. We suggest that in at least some cases the naevus has the same genetic defect(s) as generalized Darier's disease, and discuss the possibility that a patient with such a naevus could occasionally transmit Darier's disease to an offspring.- - - - - - - - - - ranking = 0.5keywords = palm (Clic here for more details about this article) |
10/43. Hidrotic ectodermal dysplasia: study of a large Chinese pedigree.Hidrotic ectodermaldysplasia was found, to our knowledge, for the first time in a Chinese family in malaysia, and it affected 15 members in five generations. The disease, which is transmitted as a non-sex-linked autosomal dominant trait, presumably originated from southern china. All 15 members had the typical nail, hair, and skin lesions, and we observed three different types of nail defects. scalp alopeica was more extensive in the female members while keratoderma of the palms and soles was more notable in the male members. The nail and skin lesions also became severer with age. Except for the infectious eczematoid dermatitis present in the propositus, none had other skin or systemic disorders. All were relatively healthy and had normal life expectancies;- - - - - - - - - - ranking = 0.5keywords = palm (Clic here for more details about this article) |
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