Kindler Syndrome

Burch, Joanna M.; Fassihi, Hiva; Jones, C. H. W.; Mengshol, Sarah; Fitzpatrick, James E.; McGrath, John A.

doi:10.1001/archderm.142.5.620

Cited by 37 publications

(5 citation statements)

References 14 publications

(29 reference statements)

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“…Our study also identifies a potential pitfall in using immunofluorescence microscopy to assist the clinical diagnosis of KS. Previously, our group has reported the usefulness of immunofluorescence microscopy on frozen skin sections in making a rapid diagnosis of KS (Ashton et al ., 2004; Fassihi et al ., 2005; Burch et al ., 2006; Arita et al ., 2007). Although it remains an invaluable tool, immunostaining of a larger number of cases now highlights that some patients with KS, with loss-of-function KIND1 mutations confirmed by gene sequencing, have almost normal anti-kindlin-1 immunostaining.…”

Section: Discussionmentioning

confidence: 99%

Colocalization of Kindlin-1, Kindlin-2, and Migfilin at Keratinocyte Focal Adhesion and Relevance to the Pathophysiology of Kindler Syndrome

Lai-Cheong

Ussar

Arita

et al. 2008

Journal of Investigative Dermatology

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Kindler syndrome (KS) results from pathogenic loss-of-function mutations in the KIND1 gene, which encodes kindlin-1, a focal adhesion and actin cytoskeleton-related protein. How and why abnormalities in kindlin-1 disrupt keratinocyte cell biology in KS, however, is not yet known. In this study, we identified two previously unreported binding proteins of kindlin-1: kindlin-2 and migfilin. Co-immunoprecipitation and confocal microscopy studies show that these three proteins bind to each other and colocalize at focal adhesion in HaCaT cells and normal human keratinocytes. Moreover, loss-of-function mutations in KIND1 result in marked variability in kindlin-1 immunolabeling in KS skin, which is mirrored by similar changes in kindlin-2 and migfilin immunoreactivity. Kindlin-1, however, may function independently of kindlin-2 and migfilin, as loss of kindlin-1 expression in HaCaT keratinocytes by RNA interference and in KS keratinocytes does not affect KIND2 or FBLIM1 (migfilin) gene expression or kindlin-2 and migfilin protein localization. In addition to identifying protein-binding partners for kindlin-1, this study also highlights that KIND1 gene expression and kindlin-1 protein labeling are not always reduced in KS, findings that are relevant to the accurate laboratory diagnosis of this genodermatosis by skin immunohistochemistry.

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Section: Discussionmentioning

confidence: 99%

Colocalization of Kindlin-1, Kindlin-2, and Migfilin at Keratinocyte Focal Adhesion and Relevance to the Pathophysiology of Kindler Syndrome

Lai-Cheong

Ussar

Arita

et al. 2008

Journal of Investigative Dermatology

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“…The clinical presentations of the two patients were compatible with the phenotypes described in previous literature. However, prior to genetic investigation, the actual subtype of EB was not differentiable by the referring clinicians due to the mimicry clinical presentation of KS to other subtypes of EB, hindering many cases of diagnosis [12] . Genetic testing in the two families helped to reach a molecular diagnosis leading to better clinical management.…”

Section: Discussionmentioning

confidence: 99%

A report and review of the recurrent c.811C>T variant and mutation spectrum of Kindler syndrome in East Asians: a diagnostic odyssey of 2 weeks versus 49 years

2023

Rare Dis Orphan Drugs J

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Kindler Syndrome (KS) is one of the rarest subtypes of epidermolysis bullosa (EB). It is characterised by congenital blistering, skin fragility, photosensitivity, and poikilodermatous skin changes. It is an autosomal recessive condition with an established disease-causing mechanism of having biallelic pathogenic variants in the FERMT1 gene. Multiple variants have been reported worldwide since the discovery in 1954. This case report describes two patients of Chinese descent with molecularly confirmed KS, one diagnosed in infancy while the other in mid-adulthood. It highlights the importance and clinical utility of diagnosing KS in children versus adults. The identification of recurrent c.811C>T variant in both patients also expedited the review of local databases and the existing mutation spectrum KS in East Asians.

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“…The histopathological features in light microscopy are nonspecific, include attenuated and flattened epidermis, hydropic alteration with cleft formation, and colloid bodies. The dermis contains dilated vessels, with dermal oedema and moderate fibrosis 5 . Transmission electron microscopy reveals major disorganization of the basement membrane, single or multiple cleavage planes at the level of the cutaneous basement membrane and reduplication of the lamina densa 4 .…”

Section: Discussionmentioning

confidence: 99%