Mutation report: identification of a germline mutation in keratin 17 in a family with pachyonychia congenita type 2. (1/84)

Pachyonychia congenita type 2 (PC-2), also known as Jackson-Lawler type PC, is an autosomal dominant disorder characterized by hypertrophic nail dystrophy associated with focal keratoderma and multiple pilosebaceous cysts. It has been demonstrated that PC-2 is associated with germline mutations in the keratin 17 (K17) gene and in its expression partner keratin 6b. In this report, we describe a novel germline mutation in K17, M88T, in a family with PC-2.  (+info)

Assignment of the gene for a new hereditary nail disorder, isolated congenital nail dysplasia, to chromosome 17p13. (2/84)

Isolated congenital nail dysplasia is an autosomal dominant disorder recently observed in a large family from southern Germany. The disorder is characterized by longitudinal streaks, thinning, and impaired formation of the nail plates leading to increased vulnerability of the free nail margins. In most cases, all fingernails and toenails are similarly involved with some accentuation of the thumb and great toenails. Histologic changes include hypergranulosis of the nail matrix and epithelial outgrowths from the nail bed. Patients do not show any alterations of hair growth and dentition, no malfunction of sweat glands and sensory organs, and no skeletal abnormalities. Isolated congenital nail dysplasia manifests from the first year of life with variable expressivity. In order to localize chromosomally the gene underlying isolated congenital nail dysplasia, linkage to the known keratin gene cluster regions on chromosomes 12q12 and 17q21 was ruled out first. The analysis of 150 microsatellite markers on various chromosomes mapped the isolated congenital nail dysplasia gene to the 6 cM interval between markers at D17S926 and D17S1528 on chromosome 17p13. Markers at D17S849, D17S 1840, and D17S1529 co-segregated completely with the isolated congenital nail dysplasia locus. The maximum two-point LOD score was found for the marker at D17S 1840 (Zmax = 6.72 at Thetamax = 0.00). The identified region harbors no currently known genes involved in skin or nail abnormalities. Isolated congenital nail dysplasia probably represents a novel isolated defect of nail development. The localization of this gene is, therefore, the first step towards the identification of a new factor in nail formation.  (+info)

A nonsense mutation in MSX1 causes Witkop syndrome. (3/84)

Witkop syndrome, also known as tooth and nail syndrome (TNS), is a rare autosomal dominant disorder. Affected individuals have nail dysplasia and several congenitally missing teeth. To identify the gene responsible for TNS, we used candidate-gene linkage analysis in a three-generation family affected by the disorder. We found linkage between TNS and polymorphic markers surrounding the MSX1 locus. Direct sequencing and restriction-enzyme analysis revealed that a heterozygous stop mutation in the homeodomain of MSX1 cosegregated with the phenotype. In addition, histological analysis of Msx1-knockout mice, combined with a finding of Msx1 expression in mesenchyme of developing nail beds, revealed that not only was tooth development disrupted in these mice, but nail development was affected as well. Nail plates in Msx1-null mice were defective and were thinner than those of their wild-type littermates. The resemblance between the tooth and nail phenotype in the human family and that of Msx1-knockout mice strongly supports the conclusions that a nonsense mutation in MSX1 causes TNS and that Msx1 is critical for both tooth and nail development.  (+info)

A genetic electrophoretic variant of human hair alpha polypeptides. (4/84)

The structural proteins of hair were solubilized by reduction of disulfide bonds in 6 M urea at alkaline pH. Following conversion of the proteins to the S-carboxy-methyl derivatives, disc electrophoresis was done in 6 M urea at pH 8.3. In about 5% of the individuals studied, a variation in the normal electrophoretic pattern was observed, and this was true of hair from different body sites. An autosomal dominant mode of inheritance was found in the four families investigated. The variant pattern was not associated with any detectable change in the color, shape, stree-strain characteristics, X-ray diffraction pattern, or amino acid composition of the hair. A similar variant pattern was also observed in nail. The most likely hypothesis is that there is a polymorphism of one of the alpha polypeptides, although a mutation of a rate-determining gene cannot be excluded.  (+info)

Nail patella syndrome: a review of the phenotype aided by developmental biology. (5/84)

Nail patella syndrome (NPS) is an autosomal dominant condition affecting the nails, skeletal system, kidneys, and eyes. Skeletal features include absent or hypoplastic patellae, patella dislocations, elbow abnormalities, talipes, and iliac horns on x ray. Kidney involvement may lead to renal failure and there is also a risk of glaucoma. There is marked inter- and intrafamilial variability. The results of a British study involving 123 NPS patients are compared with previously published studies and it is suggested that neurological and vasomotor symptoms are also part of the NPS phenotype. In addition, the first data on the incidence of glaucoma and gastrointestinal (GI) symptoms in NPS are presented. NPS is caused by loss of function mutations in the transcription factor LMX1B at 9q34. The expansion of the clinical phenotype is supported by the role of LMX1B during development.  (+info)

Trigonocephaly and associated minor anomalies in mother and son. (6/84)

A mother and her son are described with neonatal trigonocephaly, multiple suture synostosis; shallow orbits; unusual nose; deviation of the terminal phalanges of fingers 1, 2, and 5; and broad toes which radiologically may show duplication of the terminal phalanx. Untreated, the condition leads to a disfiguring oxycephaly with hypotelorism. This appears to be the first documented instance of autosomal dominant trigonocephaly. The importance of the minor anomalies in its recognition and its good prognosis are emphasized.  (+info)

Yellow-nail syndrome: report of three cases. (7/84)

The yellow nail syndrome, a combination of yellow discolouration of and dystrophic changes in the nails, pleural effusions and lymphedema, is thought to be relatively rare; to date 44 cases have been reported. Of a further three patients with this syndrome, one had all three features, one had the yellow nails alone and the other had pleural effusions and lymphedema without classic nail changes. Each had recurrent lower respiratory tract infections; and of all 47, chronic pulmonary infections occurred in approximately one quarter and were frequently associated with chronic sinus infections. The underlying abnormality is presumed to be a congenital defect of the lymphatics, but so far this has not been demonstrated to be the cause of the nail changes, the pathogenesis of which remains obscure.  (+info)

"Ingrown" nails and other toenail problems--surgical treatment. (8/84)

Appropriate office treatment for "ingrown" or deformed toenails can bring quick and lasting relief. The principle is the removal of the portion of the nail that irritates. For mild problems, a buried nail corner or spur may be successfully trimmed away without anesthesia. More extensive infection requires a nerve block anesthetic of the toe and removal of a wide triangle of deformity with nail edge and the mass of heaped up granulations. Chronic or recurrent infection is often associated with some abnormality of the nail. It usually saves time and suffering in the long run to remove a third or so of the width of the nail together with its matrix or "root." Sharp dissection is relatively easy and far more dependable than other methods of removal or destruction of the matrix. The matrix of the entire nail can be removed just as easily to eliminate such problems as the grossly thickened nail of onychogryphosis.  (+info)