1/82. 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 = focal (Clic here for more details about this article) |
2/82. A Rapp-Hodgkin like syndrome in three sibs: clinical, dental and dermatoglyphic study.Rapp-Hodgkin ectodermal dysplasia is an autosomal dominant disorder characterized by distinctive craniofacies, cleft lip or palate, oligodontia or anodontia, hypoplasia of the nails, and a decrease in or absence of the sweat glands and hair follicles. We have identified a family in which three children display clinical features similar to Rapp-Hodgkin syndrome. The father and two other sisters of the patient had normal facial features, but had short stature and had dental anomalies, the latter suggestive of ectodermal dysplasia. The overall clinical, dental, and dermatoglyphic findings of these patients are discussed in relation to reports of families with Rapp-Hodgkin syndrome.- - - - - - - - - - ranking = 54.035441845794keywords = hypoplasia (Clic here for more details about this article) |
3/82. radius hypoplasia, radial palsy, and aplasia cutis due to amniotic band syndrome.amniotic band syndrome is one of the many causes of aplasia cutis congenita. It is usually seen as a constriction band surrounding a limb or as a membrane that adheres to some part of the body. This syndrome can be associated with various malformations. An infant with amniotic adhesions producing aplasia cutis, radial palsy, and hypoplasia of the radius is presented. Early treatment led to total functional recovery of the affected limb.- - - - - - - - - - ranking = 270.17720922897keywords = hypoplasia (Clic here for more details about this article) |
4/82. 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 = focal (Clic here for more details about this article) |
5/82. 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 = focal (Clic here for more details about this article) |
6/82. Aplasia cutis congenita with precancerous transformation - the first case. Why do these scars never develop invasive tumors?The term aplasia cutis congenita characterizes a heterogeneous group of diseases which have in common a focal absence of the skin. The defect may be limited to the epidermis but often involves the full thickness of the skin including the underlying bone. At birth the lesions present as erosive patches and they heal rather rapidly with a residual scar. Although more than 200 publications on aplasia cutis congenita have appeared in the medical literature between 1966 and 1999, surprisingly no case of malignant degeneration has been described. We observed a 58-year-old male patient with aplasia cutis congenita who developed crusted changes within the scar over the past 10 years. Repeated biopsies over the years have always documented a precancerous lesion without solar elastosis. Invasion has never been observed in this patient. We hypothesize that for invasive malignancies dermal-epidermal interactions are necessary. Such a cell to cell communication seems to be impossible in patients with aplasia cutis congenita, as the dermal-epidermal unit is not developed. Aplasia cutis congenita might serve as an interesting model for further investigations on the importance of epidermal-dermal interactions.- - - - - - - - - - ranking = 1keywords = focal (Clic here for more details about this article) |
7/82. Hypohidrotic ectodermal dysplasia.Hypohidrotic ectodermal dysplasia was first described by Thurnam in 1848. It is a rare, X-linked, recessive disorder characterized by anhidrosis or hypohidrosis, hypotrichosis, dental hypoplasia and characteristic facial features. Herein, we report a typical case of hypohidrotic ectodermal dysplasia. A 20-year-old male presented with the above symptoms at birth. When a family history was taken, it was discovered that his uncle (mother's brother) had the same characteristic facial features and hypotrichosis.- - - - - - - - - - ranking = 54.035441845794keywords = hypoplasia (Clic here for more details about this article) |
8/82. Aqueductal stenosis and hydrocephalus in an infant due to aspergillus infection.Aqueductal stenosis is a common cause of hydrocephalus during infancy. We report on an infant born with aplasia cutis congenita at the scalp vertex and hypoplastic left heart syndrome developing systemic aspergillosis after cardiac surgery. The infant died at the age of 76 days despite systemic antimycotic therapy with a combination of flucytosine and amphotericin b. Therapy started at post-operative day 17 and was also applied intrathecally. Post-mortem examination revealed meningitis, multiple brain aspergillomas and microabscesses with focal ependymitis, focal bronchopneumonia, and necrotizing enterocolitis. One of the brain aspergillomas was located close to the aqueduct causing an aqueductal stenosis and an obstructive hydrocephalus. Histologically, aspergillus hyphae could only be detected in the aspergilloma of the aqueduct. To the best of our knowledge, this is the first reported case of an aqueductal stenosis caused by an aspergilloma.- - - - - - - - - - ranking = 2keywords = focal (Clic here for more details about this article) |
9/82. Cranioectodermal dysplasia: a new patient with an inapparent, subtle phenotype.Cranioectodermal dysplasia is a rare syndrome characterized by craniofacial and skeletal anomalies and ectodermal dysplasia. life-threatening associated conditions (i.e., kidney failure and abnormal regulation of the parathyroid-bone axis) can also develop. We report a patient whose features are suggestive of an inapparent, subtle phenotype of the syndrome. The patient is a 4-year-old girl with only dolichocephaly and clinodactyly; microdontia, hypodontia, and taurodontia (i.e., cone-shaped teeth); anteverted nares, full cheeks, and everted lower lip; epicanthal folds, hypertelorism and hyperopia; and corpus callosum hypoplasia. She has no rhizomelic limb shortening or hair abnormalities. In view of the rarity of the cranioectodermal dysplasias, the variability of the phenotype, and the uncertain outcome of some previously described patients, we believe this inapparent, subtle case should reported to enable better understanding and treatment of this rare syndrome.- - - - - - - - - - ranking = 54.035441845794keywords = hypoplasia (Clic here for more details about this article) |
10/82. Bilateral nephroblastoma in familial Hay-Wells syndrome associated with familial reticulate pigmentation of the skin.We report on a girl with maxillary hypoplasia, prominent ears, dry sparse hair, palmar and plantar keratoderma, dystrophic nails, patchy pigmented skin lesions in hands and feet and bilateral wilms tumor. She was born with bilateral ankyloblepharon. The mother and maternal grandmother presented similar ectodermal defects. skin biopsies of the patient and her mother proved to contain cells overexpressing p63 by immunohistochemistry. Karyotypes of the patient and her mother, and FISH studies on lymphocytes and tumor cells of the girl demonstrated a mosaic 11p15.5 deletion. These findings suggest a relationship between familial ankyloblepharon, ectodermal defects and cleft lip and palate (AEC) syndrome (Hay-Wells syndrome) and familial reticulate pigmentation of the skin. In addition the development of wilms tumor and 11p15.5 region involvement expand the genetic relationship between these conditions and the enlarging group of genetic entities related to nephroblastoma.- - - - - - - - - - ranking = 54.035441845794keywords = hypoplasia (Clic here for more details about this article) |
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