1/76. 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 = ectodermal dysplasia, dysplasia (Clic here for more details about this article) |
2/76. 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 = 1keywords = ectodermal dysplasia, dysplasia (Clic here for more details about this article) |
3/76. prevalence and new phenotypic and radiologic findings in congenital onychodysplasia of the index finger.Congenital onychodysplasia of the index finger (COIF) is a rare condition characterized by dysplastic changes in the nail with variable phenotypic manifestations. Its prevalence is unknown. We describe three newborn patients with various clinical and radiologic expressions of this entity. The first, born to a mother treated with multiple antidepressant drugs, had bilateral nail dysplasia of the index finger without bony involvement. The second presented with bilateral hypoplastic nail of the index finger and bilateral symphalangism of the fifth finger; aplastic distal phalanges of the second finger was also noted radiologically. The third baby (born to a diabetic mother treated with insulin), had micronychia and brachydactyly of the right index finger and syndactyly of the second and third fingers; the radiologic finding was bilateral brachymesophalangia of the index finger. It would seem that, besides the nail dysplasia of the index finger, COIF may also be associated with bone dysplasia of the same finger.- - - - - - - - - - ranking = 0.034008439340721keywords = dysplasia (Clic here for more details about this article) |
4/76. 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 = 1keywords = ectodermal dysplasia, dysplasia (Clic here for more details about this article) |
5/76. 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 = 1keywords = ectodermal dysplasia, dysplasia (Clic here for more details about this article) |
6/76. Hereditary hypodontia and onychorrhexis of the fingernails and toenail koilonychia: Witkop's tooth-and nail syndrome.The tooth-and-nail syndrome (Witkop's syndrome) is a rare autosomal dominant ectodermal dysplasia manifest by defects of the nail plates of the fingers and toes and hypodontia with normal hair and sweat gland function. We report a thirteen year-old girl who presented with marked longitudinal ridging of the nail plates of all ten fingers. The toenails were mildly ridged with koilonychia. Her mother's fingers were similarly affected to a lesser degree while her toenails appeared normal. Examination of the child's dentition revealed a hyperplastic frenulum and the absence of one of the usual four mandibular incisors. history provided by the mother described the maternal grandmother and maternal great aunt as having identical nail findings and the presence of only three lower incisors. hair examination was normal in the mother and child, and no history or findings of sweat gland dysfunction was present. This report describes familial hypodontia, fingernail onychorrhexis, and toenail koilonychia consistent with Witkop's syndrome.- - - - - - - - - - ranking = 1keywords = ectodermal dysplasia, dysplasia (Clic here for more details about this article) |
7/76. Congenital onychodysplasia of the index finger: Iso and Kikuchi syndrome.A new case of unilateral congenital onychodysplasia of the index finger outside japan is reported.- - - - - - - - - - ranking = 0.021255274587951keywords = dysplasia (Clic here for more details about this article) |
8/76. Witkop tooth and nail syndrome: report of two cases in a family.tooth and nail syndrome, an autosomal dominant condition, is characterized by hypodontia and nail dysplasia. Mandibular incisors, second molars and maxillary canines are the most frequently missing teeth. tooth shape may vary and conical and narrow crowns are common. Nail dysplasia affects fingernails and toenails and is often more severe in childhood. nails may be spoon-shaped, ridged, slow growing and easily broken. The clinical and radiographic features of a father and son presenting with this rare condition are described.- - - - - - - - - - ranking = 0.0085021098351803keywords = dysplasia (Clic here for more details about this article) |
9/76. Ellis van Creveld syndrome (chondroectodermal dysplasia, MIM 22550) in three siblings from a non-consanguineous mating.The major diagnostic features of Ellis van Creveld syndrome (EvC) includes disproportionate short stature, polydactyly, ectodermal anomalies, and structural heart defects. We describe three siblings with EvC of a non-consanguineous mating. The history of these siblings well illustrate the clinical manifestations and complications that children with EvC encounter. All three girls had short stature, narrow rib cage, polydactyly and nail hypoplasia. The first daughter died in early infancy in respiratory failure. The second daughter underwent open heart surgery for atrial septal defect repair. The third daughter, diagnosed in utero with fetal ultrasonography, currently is scheduled for surgical excision of extra-digits and extraction of neonatal teeth. infant mortality rates among patients with EvC is strikingly high due primarily to cardiorespiratory failure. If they survive infancy morbidity is significant. The gene effected in individuals with EvC has recently been identified on the short arm of chromosome 4. Future testing for gene mutations may provide valuable information for premarital counseling and prenatal diagnosis. Three offspring with disproportionate short stature, polydactyly, and ectodermal dysplasia of a non-consanguineous mating, strongly indicate parental heterozygosity for Ellis van Creveld syndrome.- - - - - - - - - - ranking = 5keywords = ectodermal dysplasia, dysplasia (Clic here for more details about this article) |
10/76. 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 = 0.025506329505541keywords = dysplasia (Clic here for more details about this article) |
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