1/110. 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 = congenita (Clic here for more details about this article) |
2/110. 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 = congenita (Clic here for more details about this article) |
3/110. Circumferential fingernail.We describe a Brazilian girl with a congenital circumferential nail on her left ring finger associated with other bony and soft tissue abnormalities of the affected limb. The tubular nail plate resembling a punch biopsy has been described as a circumferential nail, an extremely rare congenital malformation that can be associated with other congenital anomalies. In our review of the literature, there have only been two previous reports of this unusual condition affecting the fingernails.- - - - - - - - - - ranking = 0.6keywords = congenita (Clic here for more details about this article) |
4/110. The wide spectrum of clinical expression in Adams-Oliver syndrome: a report of two cases.Two children are described with the combination of aplasia cutis congenita (ACC) and transverse limb defects known as Adams-Oliver syndrome. Whereas in the first child the typical features of ACC, syndactyly and transverse nail dystrophy were only mildly expressed and associated defects of the central nervous system and cardiac malformations were absent, the second child suffered from a very severe expression of the syndrome, with a combination of ACC, syndactyly, cutis marmorata telangiectatica congenita and multiple cardiac and central nervous system malformations which resulted in fatal central respiratory insufficiency.- - - - - - - - - - ranking = 0.4keywords = congenita (Clic here for more details about this article) |
5/110. 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 = 0.8keywords = congenita (Clic here for more details about this article) |
6/110. 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 = congenita (Clic here for more details about this article) |
7/110. A case of pachyonychia congenita with oral leukoplakia and steatocystoma multiplex.Pachyonchia congenita (PC) is an uncommon autosomal dominant genodermatosis affecting the nails and other ectodermal tissues. The most striking features are symmetrically thickened dysmorphic nails and hyperkeratotic skin lesions. We report a case of pachyonychia congenita in a 30-year-old male patient who had thickening and gray-brown discoloration of all nails and many nodules on his back and neck. He also had hyperkeratotic skin lesions on both feet. His tongue had irregularly-shaped, whitish plaques. histology of these nodules revealed the characteristic features of steatocystoma multiplex. After treatment with oral retinoic acid, his hyperkeratotic skin lesions improved.- - - - - - - - - - ranking = 1.2keywords = congenita (Clic here for more details about this article) |
8/110. 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 = congenita (Clic here for more details about this article) |
9/110. 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 = 0.2keywords = congenita (Clic here for more details about this article) |
10/110. 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 = 0.2keywords = congenita (Clic here for more details about this article) |
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