Skin pigmentary anomalies and mosaicism for an acentric marker chromosome originating from 3q.
We report on a 22 year old man with hyperpigmentation distributed along the lines of Blaschko in whom cytogenetic analysis showed mosaicism for an unusual supernumerary marker chromosome. The patient was of normal intelligence and was not dysmorphic. The marker was present in 30% of his lymphocytes and in 6% of his skin fibroblasts from a dark area, while fibroblasts from a light area showed a normal karyotype, 46,XY. We have identified the origin of the marker using fluorescence in situ hybridisation (FISH) with whole chromosome painting probes and YAC specific clones. The marker was found to consist of duplicated chromosome material from the distal part of chromosome 3q and was interpreted as inv dup(3)(qter-->q27.1::q27.1-->qter). Hence, this marker did not include any known centromeric region and no alpha satellite DNA could be detected at the site of the primary constriction. The patient was therefore tetrasomic for 3q27-q29 in the cells containing the marker chromosome. We postulate that, in our case, pigmentary anomalies may result directly from the gain of specific pigmentation genes localised on chromosome 3q. (+info)
Effects of renal transplantation on hearing and ocular changes in a monozygotic twin with Alport's syndrome: comparison with other twin on hemodialysis.
AIM: To present a unique case of Alport's syndrome in monozygotic twins with two different treatment modalities - renal transplantation and hemodialysis, and to evaluate the effects of therapy on hearing and ophthalmological findings. METHODS: Pure-tone audiogram and ophthalmologic examinations were performed in both twins at the age of 30. At the age of 46, 4 years after renal transplantation in the first twin and after 6 years of hemodialysis in the second twin, both twins underwent control audiometric and ophthalmologic examinations. RESULTS: Control audiometric measurements showed the progression of bilateral sensorineural hearing loss in the high-frequency range (>2,000 Hz) in both twins. The hearing threshold progressed from initial 50 dB in both twins at the time of the diagnosis to 55 dB in the twin on hemodialysis, and 85 dB in the twin with a transplanted kidney. Retinal blurry hyperpigmentations disappeared in the twin with a transplanted kidney. CONCLUSION: In comparison with hemodialysis, renal transplantation in Alport's syndrome may have deleterious effect on hearing, when associated with plasma hyperviscosity and hyperlipidemia, but may lead to regression of retinal hyperpigmentation. (+info)
NEMO/IKK gamma-deficient mice model incontinentia pigmenti.
Disruption of the X-linked gene encoding NF-kappa B essential modulator (NEMO) produces male embryonic lethality, completely blocks NF-kappa B activation by proinflammatory cytokines, and interferes with the generation and/or persistence of lymphocytes. Heterozygous female mice develop patchy skin lesions with massive granulocyte infiltration and hyperproliferation and increased apoptosis of keratinocytes. Diseased animals present severe growth retardation and early mortality. Surviving mice recover almost completely, presumably through clearing the skin of NEMO-deficient keratinocytes. Male lethality and strikingly similar skin lesions in heterozygous females are hallmarks of the human genetic disorder incontinentia pigmenti (IP). Together with the recent discovery that mutations in the human NEMO gene cause IP, our results indicate that we have created a mouse model for that disease. (+info)
The role of the epidermal endothelin cascade in the hyperpigmentation mechanism of lentigo senilis.
Little is known about the mechanism(s) underlying hyperpigmentation in lentigo senilis. We have previously reported that keratinocyte-derived endothelins are intrinsic paracrine mitogens and melanogens for human melanocytes and that they play an essential role in stimulating ultraviolet-B-induced melanogenesis. In this study, we have used immunohistochemistry and reverse transcriptase polymerase chain reaction analysis to clarify the role of the endothelin cascade, including endothelin production, processing by endothelin-converting enzyme, and expression of the endothelin B receptor, in the hyperpigmentary mechanism(s) involved in lentigo senilis. The number of tyrosinase immunopositive melanocytes in lentigo senilis lesional skin was increased 2-fold over the perilesional epidermis. Immunohistochemistry using antibodies to endothelin-1 demonstrated relatively stronger staining in the lesional epidermis than in the perilesional epidermis. Reverse transcriptase polymerase chain reaction analysis concomitantly demonstrated accentuated expression of transcripts for endothelin-1 and for the endothelin B receptor in lentigo senilis lesional skin, which was accompanied by a similar accentuated expression of tyrosinase mRNA compared with the perilesional control. The endothelin-1-inducible cytokine, tumor necrosis factor alpha, was consistently upregulated in the lentigo senilis lesional epidermis as determined at the transcriptional level and by immunostaining, whereas interleukin-1alpha was downregulated. In contrast, endothelin-converting enzyme 1alpha mRNA was not substantially increased in the lesional epidermis. These findings suggest that an accentuation of the epidermal endothelin cascade, especially with respect to expression of endothelin and the endothelin B receptor, plays an important role in the mechanism involved in the hyperpigmentation of lentigo senilis. (+info)
Short wavelength automated perimetry in age related maculopathy.
BACKGROUND/AIMS: Previous studies reported the predictive value of the short wavelength sensitive (SWS) cone mediated sensitivity for visual outcome in age related macular degeneration. In this study SWS sensitivity was measured by commercially available blue on yellow perimetry in patients with non-exudative age related maculopathy (ARM) and compared with the presence of morphological risk factors and the status of the fellow eye. METHODS: In a prospective cross sectional study, 126 patients (57 males, 69 females, mean age 71 (SD 6) years) with ARM (visual acuity >20/50) were tested. Central visual fields (blue on yellow) were obtained with a conventional perimeter. Fundus slides were graded by two independent observers for soft drusen and presence of focal hyperpigmentation. RESULTS: Mean sensitivity and standard deviation of all patients exhibited a significant reduction with age. Patients with soft drusen had significantly lower sensitivity than those without, whereas there were no differences in visual acuity (log MAR). Sensitivity was also reduced in those eyes with fellow eyes having a sight threatening complication of age related macular degeneration (AMD). Eyes with focal hyperpigmentation compared with those without had no loss of sensitivity, but did have a significant decrease in the central part of the field compared with the more eccentric. CONCLUSION: SWS sensitivity loss is associated with common risk factors for progression to AMD. Short wavelength automated perimetry is moderately rapid and readily available. It may serve as a tool in future ARM trials. (+info)
Refined mapping of Naegeli-Franceschetti- Jadassohn syndrome to a 6 cM interval on chromosome 17q11.2-q21 and investigation of candidate genes.
Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis are autosomal dominant ectodermal dysplasias characterized by the absence of dermatoglyphics, reticulate hyper pigmentation of the skin, hypohidrosis, and heat intolerance. Palmoplantar keratoderma, nail dystrophy, and enamel defects are common in Naegeli-Franceschetti-Jadassohn syndrome, whereas diffuse alopecia is only seen in dermatopathia pigmentosa reticularis. We studied a large Swiss family with Naegeli-Franceschetti-Jadassohn syndrome originally described by Naegeli in 1927 and assessed linkage to chromosome 17q, which was proposed to harbor the Naegeli-Franceschetti-Jadassohn syndrome gene. Our results considerably narrow the Naegeli-Franceschetti-Jadassohn syndrome gene region from 27 cM to 6 cM flanked by D17S933 and D17S934 with a maximum multipoint LOD score of 2.7 at marker locus D17S800. In addition, we studied a small family with dermatopathia pigmentosa reticularis, and our linkage data suggest that dermatopathia pigmentosa reticularis may map to the same chromosomal region. The Naegeli-Franceschetti-Jadassohn syndrome critical interval spans approximately 5.4 Mb and contains a minimum of 45 distinct genes. We scrutinized 13 new prime candidates in addition to five genes previously examined, established the genomic organization of 10 of these genes, and excluded all of them by mutation analysis. Moreover, we identified a cDNA (KRT24) encoding a new keratin protein that bears high similarity to the type I keratins and displays a unique expression profile. No pathogenic mutations were identified in this novel gene either, however. In summary, our results substantially refine the Naegeli-Franceschetti-Jadassohn syndrome region and will aid in identifying a gene that is critical for ontogenesis of multiple ectodermal tissues. (+info)
Role of dermal melanocytes in cutaneous pigmentation of stasis dermatitis: a histopathological study of 20 cases.
Stasis dermatitis is an itchy, scaly, and hyperpigmented condition of the lower leg due to venous insufficiency. Hemosiderin and/or melanin have been considered responsible for the brown pigmentation. However, there are not sufficient histopathologic studies. In this retrospective study the hospital records and biopsy slides of 20 patients were reviewed to determine the pathogenetic mechanisms of brown pigmentation in stasis dermatitis. Fifteen were men (75%) and 5 were women (25%) with a mean age of 46.2+/-8.2 yr (18-76), mean age at onset of 43.4+/-18.0 yr (17-73), and a mean duration of the disease 2.8+/-2.5 yr (0.25-10). All patients had varicose vein and complained of pruritus. On histopathologic evaluation, two cases out of 20 (3 skin biopsy specimens from 25 samples) showed dermal melanocytes containing melanin, and incontinence of melanin pigment was observed in 5 cases, which indicates that melanin pigments from epidermis could contribute to cutaneous pigmentation in stasis dermatitis. However, the existence of dermal melanocytes in two cases cannot be explained because normally the dermis contains no melanocytes. Further studies concerning the role of iron or inflammatory cytokines on the development of dermal melanocytes should be conducted. (+info)
Aloin, cinnamic acid and sophorcarpidine are potent inhibitors of tyrosinase.
OBJECTIVE: To evaluate the effects of aloin, cinnamic acid and 15 other kinds of natural chemicals on the activity of tyrosinase, in order to provide lightening agents in the treatment of hyperpigmentation disorders and cosmetic additives. METHODS: Tyrosinase activity was estimated by measuring the oxidation rate of L-dopa. Inhibition of the enzyme was deduced according to the Lineweaver-Burk plots compared to the control. RESULTS: Cadabine, paeonal, farrerol, evodin, cinnamic acid, aloin and sophorcarpidine had different levels of inhibition of tyrosinase. The inhibitory rates of cinnamic acid (2 mmol/L, 0.5 mmol/L), aloin (2 mmol/L) and the rest were significantly higher than that of hydroquinone (0.5 mmol/L) (P < 0.05). CONCLUSIONS: Tyrosinase activity can be greatly inhibited by cinnamic acid, aloin and sophorcarpidine, of which sophorcarpidine functions as an uncompetitive inhibitor, compared to aloin and cinnamic acid, which are mixed-type inhibitors. (+info)