Bart-Pumphrey syndrome (BPS) is an autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, which show considerable phenotypic variability. The ...Bart-Pumphrey syndrome (BPS) is an autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, which show considerable phenotypic variability. The clinical features partially overlap with Vohwinkel syndrome and Keratitis-chthyosis-Deafness syndrome,both disorders caused by dominant mutations in the GJB2 gene encoding the gap junction protein connexin-26, suggesting an etiological relationship. We report here a novel GJB2 mutation N54K segregating in a family with BPS, which was not detected in 110 control individuals of Northern European ancestry. This non- conservative missense mutation lies within a cluster of pathogenic GJB2 mutations affecting the evolutionary conserved first extracellular loop of Cx26 important for docking of connexin hemichannels and voltage gating. Immunostaining of Cx26 in lesional palmar and knuckle skin was weak or absent, although its adnexal expression appeared normal and the punctate membrane staining of Cx26 and other epidermal connexins was not altered. Nevertheless, the widespread immunostaining of Cx30 throughout the spinous cell layers suggested a compensatory overexpression. Our results emphasize that pleiotropic GJB2 mutations are responsible for at least 5 overlapping dermatological disorders associated with syndromic hearing loss and cover a wide range of severity and organ involvement.展开更多
Netherton syndrome (NS) is a severe autosomal recessive ichthyosis. It is characterized by congenital ichthyosiform erythroderma, trichorrhexis invaginata, ichthyosis linearis circumflexa, atopic diathesis and frequen...Netherton syndrome (NS) is a severe autosomal recessive ichthyosis. It is characterized by congenital ichthyosiform erythroderma, trichorrhexis invaginata, ichthyosis linearis circumflexa, atopic diathesis and frequent bacterial infections. Pathogenic mutations in SPINKS have recently been identified in NS. SPINKS encodes lymphoepithelial Kazal-type-related inhibitor (LEKTI), a new type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. We report two Taiwan Residents brothers with NS. The patients had typical manifestations of NS with an atopic diathesis and recurrent staphylococcal infections, including staphylococcal scalded skin syndrome (SSSS) since birth. Horny layers were obtained by skin surface biopsy for electron microscopy from lesional skin of both patients and from normal controls. All 33 exons and flanking intron boundaries of SPINKS were amplified for direct sequencing. The ultrastructure of the stratum corneum (SC) was characterized by premature degradation of corneo desmosomes (CDs) with separation of corneocytes. A homozygous 2260A→ T (K754X) mutation of SPINK5 was found in both patients. Staphylococcal exfoliative toxin A (ETA) is a serine protease capable of cleaving desmoglein 1, an important adhesive molecule of CDs, and can cause separation of the SC, resulting in SSSS. The premature degradation of CDs found in our patients may be attributable to insufficient LEKTI, and possibly also to colonization/infection of ETA-producing Stophylococcus aureus. Mechanisms involved in the pathogenesis of the skin barrier defect in NS are proposed. Further study is needed to prove this hypothesis.展开更多
Background: Loss of visual acuity due to ischemic retinal vein occlusion (RVO) is still a major problem in ophthalmology. Prognosis is poor and loss of vision is a severe risk. New approaches for treatment like system...Background: Loss of visual acuity due to ischemic retinal vein occlusion (RVO) is still a major problem in ophthalmology. Prognosis is poor and loss of vision is a severe risk. New approaches for treatment like systemic fibrinolysis and s urgical procedures have been suggested. Patients and Methods: In a clinical tria l 8 patients with ischemic CRVO underwent surgical decompression. Strict criteri a of inclusion were maintained. Radial optic neurotomy (RON) was performed 0.25 -5 months after retinal vein occlusion. Follow up-time was 3 months. Visual ac uity and incidence of typical complications after RVO were the main points of in terest in our scientific evaluation. Results: Visual acuity improved significant ly after the surgical procedure. For ischemic CRVO EDTRS charts increased from l ogMAR 1.0 (decimal 0.17) to 0.68 (0.30) at 3 months after surgery. Surgical or e arly complications did not occur within 3 months. The recovery of retinal blood flow during fluorescein angiography was investigated in 75%of the patients. A r esolution of non perfusion-areas could be detected in 50%of the eyes. Conclusi ons: For patients with retinal vein occlusion RON seems to be a safe and feasibl e procedure. The results indicate the potential to improve visual acuity while t ypical complications due to surgery or vein occlusion did not occur during the f irst three months.展开更多
文摘Bart-Pumphrey syndrome (BPS) is an autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, which show considerable phenotypic variability. The clinical features partially overlap with Vohwinkel syndrome and Keratitis-chthyosis-Deafness syndrome,both disorders caused by dominant mutations in the GJB2 gene encoding the gap junction protein connexin-26, suggesting an etiological relationship. We report here a novel GJB2 mutation N54K segregating in a family with BPS, which was not detected in 110 control individuals of Northern European ancestry. This non- conservative missense mutation lies within a cluster of pathogenic GJB2 mutations affecting the evolutionary conserved first extracellular loop of Cx26 important for docking of connexin hemichannels and voltage gating. Immunostaining of Cx26 in lesional palmar and knuckle skin was weak or absent, although its adnexal expression appeared normal and the punctate membrane staining of Cx26 and other epidermal connexins was not altered. Nevertheless, the widespread immunostaining of Cx30 throughout the spinous cell layers suggested a compensatory overexpression. Our results emphasize that pleiotropic GJB2 mutations are responsible for at least 5 overlapping dermatological disorders associated with syndromic hearing loss and cover a wide range of severity and organ involvement.
文摘Netherton syndrome (NS) is a severe autosomal recessive ichthyosis. It is characterized by congenital ichthyosiform erythroderma, trichorrhexis invaginata, ichthyosis linearis circumflexa, atopic diathesis and frequent bacterial infections. Pathogenic mutations in SPINKS have recently been identified in NS. SPINKS encodes lymphoepithelial Kazal-type-related inhibitor (LEKTI), a new type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. We report two Taiwan Residents brothers with NS. The patients had typical manifestations of NS with an atopic diathesis and recurrent staphylococcal infections, including staphylococcal scalded skin syndrome (SSSS) since birth. Horny layers were obtained by skin surface biopsy for electron microscopy from lesional skin of both patients and from normal controls. All 33 exons and flanking intron boundaries of SPINKS were amplified for direct sequencing. The ultrastructure of the stratum corneum (SC) was characterized by premature degradation of corneo desmosomes (CDs) with separation of corneocytes. A homozygous 2260A→ T (K754X) mutation of SPINK5 was found in both patients. Staphylococcal exfoliative toxin A (ETA) is a serine protease capable of cleaving desmoglein 1, an important adhesive molecule of CDs, and can cause separation of the SC, resulting in SSSS. The premature degradation of CDs found in our patients may be attributable to insufficient LEKTI, and possibly also to colonization/infection of ETA-producing Stophylococcus aureus. Mechanisms involved in the pathogenesis of the skin barrier defect in NS are proposed. Further study is needed to prove this hypothesis.
文摘Background: Loss of visual acuity due to ischemic retinal vein occlusion (RVO) is still a major problem in ophthalmology. Prognosis is poor and loss of vision is a severe risk. New approaches for treatment like systemic fibrinolysis and s urgical procedures have been suggested. Patients and Methods: In a clinical tria l 8 patients with ischemic CRVO underwent surgical decompression. Strict criteri a of inclusion were maintained. Radial optic neurotomy (RON) was performed 0.25 -5 months after retinal vein occlusion. Follow up-time was 3 months. Visual ac uity and incidence of typical complications after RVO were the main points of in terest in our scientific evaluation. Results: Visual acuity improved significant ly after the surgical procedure. For ischemic CRVO EDTRS charts increased from l ogMAR 1.0 (decimal 0.17) to 0.68 (0.30) at 3 months after surgery. Surgical or e arly complications did not occur within 3 months. The recovery of retinal blood flow during fluorescein angiography was investigated in 75%of the patients. A r esolution of non perfusion-areas could be detected in 50%of the eyes. Conclusi ons: For patients with retinal vein occlusion RON seems to be a safe and feasibl e procedure. The results indicate the potential to improve visual acuity while t ypical complications due to surgery or vein occlusion did not occur during the f irst three months.
