Prenatal diagnosis of oculocutaneous albinism by electron microscopy of fetal skin.

Oculocutaneous albinism was diagnosed prenatally by electron microscopic examination of fetal skin samples taken during fetoscopy at 20 weeks of gestation. Melanosome development in hair bulb melanocytes progressed no further than stage II, indicating a lack of melanin synthesis. In 4 age-matched control fetuses, numerous stage IV melanosomes, signifying active melanin synthesis, were identified. The diagnosis was confirmed after the pregnancy was terminated at 22 weeks. Examination of the fetal eye showed absence of pigment in the retinal epithelium and uvea at a stage when ocular melanogenesis would normally be active. This study shows that oculocutaneous albinism can be detected in the second trimester using similar techniques to those employed in the prenatal diagnosis of epidermolysis bullosa and ichthyosis.

Rapid prenatal diagnosis and exclusion of epidermolysis bullosa using novel antibody probes.

Prenatal diagnosis of recessive dystrophic epidermolysis bullosa was successfully achieved at 19 weeks' gestation by indirect immunofluorescence examination of a fetal skin biopsy sample using the monoclonal antibody LH 7:2. The abortus displayed marked blistering and the diagnosis was confirmed by transmission electron microscopy (TEM). In 3 further pregnancies at risk for lethal junctional epidermolysis bullosa the diagnosis was excluded using the polyclonal antibody AA3. In all these studies the results were available within 4 h of receiving the samples. These new techniques offer a quick and simple alternative to TEM for midtrimester prenatal diagnosis of 2 severe recessive forms of epidermolysis bullosa.

Rapid processing of fetal skin for prenatal diagnosis by light and electron microscopy.

A method has been developed for rapid processing of fetal skin for prenatal diagnosis of hereditary skin diseases by light and electron microscopy. Fixation, dehydration, embedding, and polymerisation can be achieved in about 5 h. The quality of tissue preservation compares favourably with that produced by slower conventional techniques. This procedure may provoke a wider interest in the potential use of fetal skin biopsy in prenatal diagnosis, especially if identification of structural abnormalities is a feasible alternative to more time consuming biochemical analysis.

Prenatal diagnosis of bullous ichthyosiform erythroderma: detection of tonofilament clumps in fetal epidermal and amniotic fluid cells.

The prenatal diagnosis of bullous ichthyosiform erythroderma (BIE) has been achieved at 20 weeks' gestation by electron microscopic identification of a pathognomonic cytoskeletal abnormality within fetal epidermal cells obtained by fetoscopic skin biopsy. The same abnormality was also observed in skin derived amniotic fluid cells. The question whether amniocentesis might be used instead of fetoscopy for future prenatal detection of BIE is discussed.

Epidermolysis bullosa acquisita antigen and the carboxy terminus of type VII collagen have a common immunolocalization to anchoring fibrils and lamina densa of basement membrane.

In this study a variety of immunoelectron microscopic methods were used to define the precise ultrastructural binding site of epidermolysis bullosa acquisita antibodies (EBA-Ab). We used two EBA sera which immunoblotted with the same skin-extracted protein as that labelled by a monoclonal antibody (LH7.2) which is known to react with the carboxy terminus of type VII collagen. Gold-conjugated antibodies were used in two different immunoelectron microscopic procedures to compare the labelling characteristics of EBA-Ab and LH7.2 in normal human skin. Antibody incubations were performed using ultra-thin cryosections of unfixed skin and thin slices of fresh skin (en bloc technique) before conventional fixation and embedding in Epon. Both methods showed similar labelling features for both EBA-Ab and LH7.2. With ultra-thin cryosections there was labelling of the lamina densa and an undefined component of the sublamina densa region. With the en bloc technique, labelling of dermal ends of anchoring fibrils and of amorphous material recently defined as 'anchoring plaques' was evident. There was no labelling of the central banded portions of anchoring fibrils. We conclude that EBA-Ag is localized to the dermal ends of anchoring fibrils in addition to the lamina densa and possibly anchoring plaques, and thus has the same distribution as the carboxy terminus of type VII collagen.