Prenatal diagnosis of herlitz junctional epidermolysis bullosa by amniocentesis

Abstract

Herlitz junctional epidermolysis bullosa (HJEB) is a severe blistering disorder which usually results in death during infancy. We have previously shown that the anchoring filament protein laminin-5 (kalinin/nicein), which mediates keratinocyte attachment and dermal-epidermal cohesion, is abnormally expressed in individuals with HJEB. Laminin-5 was detected by Western blot analysis in amniotic fluid from 44 consecutive normal second-trimester control pregnancies, but was undetectable in second-trimester amniotic fluid from four pregnancies with fetuses affected by HJEB. In one case of severe non-Herlitz JEB, laminin-5 was detected in both amniotic fluid and skin. In human amniotic fluid, the laminin-5 a3 subunit was processed to a major 165 kD species and a minor 145 kD species and the beta 2 subunit was partially processed to 105 kD. Although laminin-5 was covalently associated with laminin-6 (K-laminin) in amniotic membrane, no covalent interaction was detected in amniotic fluid. Laminin-5 from amniotic fluid strongly supported keratinocyte attachment. These results suggest that Western blot analysis of second-trimester amniotic fluid is useful in determining the prenatal diagnosis of HJEB and that laminin-5 may serve a physiologically important function in amniotic fluid.

Junctional epidermolysis bullosa gravis (Herlitz): diagnostic and genetic aspects

“…JEBH is a congenital blistering disease with an unfavourable prognosis. Mutations of the genes encoding for laminin 5 subunits causing defective hemidesmosomes responsible for severe blistering have been shown in several cases 1–4 . In the present case two mutations were detected in exon 14 of LAMB3 – the recurrent mutation R635X (maternal) and the novel mutation 1629insG (paternal).…”

“…Epidermolysis bullosa (EB) is a heterogeneous group of hereditary blistering skin diseases with different aetiology, inheritance, phenotypes, histomorphology (intraepidermal, junctional, intradermal blisters) and prognosis 1–4 …”

“…Epidermolysis bullosa (EB) is a heterogeneous group of hereditary blistering skin diseases with different aetiology, inheritance, phenotypes, histomorphology (intraepidermal, junctional, intradermal blisters) and prognosis. [1][2][3][4] The junctional epidermolysis bullosa gravis (JEBH) (Herlitztype) (OMIM 226700) is a rare autosomal-recessive disease with lethal prognosis. The incidence is about 1 in 200 000.…”

Retrospective evidence on outcomes and experiences of pregnancy and childbirth in epidermolysis bullosa in Australia and New Zealand

“…The bulk of the available literature is mainly on prenatal diagnosis of severe forms of EB (EBS or JEB with pyloric atresia, Herlitz JEB, and RDEB) and its role in management decisions such as termination (D’Alessio et al, 2008, Marinkovich et al, 1995, Norup 1999, Pfendner et al, 2003, Yan et al, 2007). A survey performed in Denmark amongst obstetricians and pediatricians showed that in the case of newborns with severe EB, there was a strong consensus to withhold life-prolonging treatment, reflecting attitudes to EB (Norup 1999).…”

Mutation-Based Prenatal Diagnosis of Herlitz Junctional Epidermolysis Bullosa

“…There has been a demand for prenatal diagnosis from families who have had a previous affected child with EB, particularly those with H-JEB, due to the life-threatening complications and significant long-term morbidity. Until recently, fetal skin biopsy was the only method of prenatal diagnosis available to families at risk for recurrence of H-JEB, although detection of laminin 5 from amniotic fluid has been attempted (Marinkovich et al, 1995). Initially, skin biopsies were performed by direct fetoscopic visualization, but more recent advances have utilized biopsy forceps under ultrasound guidance.…”