Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis.

Background: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of skin disorders. Several mutant genes have been identified in ARCI, but the association between genotype and phenotype is poorly understood.

Methods: To investigate genotype-phenotype correlations in ARCI, we selected 27 patients from 18 families with specific ultrastructural features of the epidermis.

Ullrich congenital muscular dystrophy: connective tissue abnormalities in the skin support overlap with Ehlers-Danlos syndromes.

Ullrich congenital muscular dystrophy (UCMD) is caused by mutations in the three genes coding for the alpha chains of collagen VI and characterized by generalized muscle weakness, striking hypermobility of distal joints in conjunction with variable contractures of more proximal joints, and normal intellectual development. The diagnosis is supported by abnormal immunoreactivity for collagen VI on muscle biopsies. As patients with UCMD show clinical characteristics typical of classical disorders of connective tissue such as Ehlers-Danlos syndromes (EDS), we investigated the ultrastructure of skin biopsy samples from patients with UCMD (n=5).

Analysis of the LAMB3 gene in a junctional epidermolysis bullosa patient reveals exonic splicing and allele-specific nonsense-mediated mRNA decay.

How splicing, the process of intron removal in pre-messenger RNA (mRNA), is carried out with such fidelity in human cells is still not understood, although some general rules are being proposed mainly by in vitro experiments. These rules are currently being redefined by analysis of splicing mechanisms in patients presenting splicing defects. We analysed material of a patient suffering from junctional epidermolysis bullosa, a heritable blistering skin disease.

A site-specific plectin mutation causes dominant epidermolysis bullosa simplex Ogna: two identical de novo mutations.

Plectin is one of the largest and most versatile cytolinker proteins known. In basal keratinocytes it links the intermediate filament network to cell membrane-associated hemidesmosomes. Several mutations in its gene have been identified that lead to the recessive disease epidermolysis bullosa with muscular dystrophy.

Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling.

Lysosomal cysteine proteinases of the papain family are involved in lysosomal bulk proteolysis, major histocompatibility complex class II mediated antigen presentation, prohormone processing, and extracellular matrix remodeling. Cathepsin L (CTSL) is a ubiquitously expressed major representative of the papain-like family of cysteine proteinases. To investigate CTSL in vivo functions, the gene was inactivated by gene targeting in embryonic stem cells.