Diagnosis of merosin (laminin-2) deficient congenital muscular dystrophy by skin biopsy

Abstract

Summary Background The α2 chain of laminin-2 (merosin), encoded by a gene on chromosome 6q22, is deficient in about half the cases of congenital muscular dystrophy. Diagnosis of this condition has relied on immunocytochemical analysis of the α2 chain in muscle biopsy specimens. We have observed that normal skin also expresses laminin α2 in the basement membrane at the junction of the dermis and epidermis. Here we have investigated laminin α2 deficiency in skin biopsy specimens from two patients with congenital muscular dystrophy. Participants Two patients with severe congenital muscular dystrophy gave informed consent to a skin biopsy. The girl was aged 10 and the boy was aged 7. The specimens were labelled with a commercially available mouse monoclonal antibody and a rat monoclonal antibody (4H8-2), which recognise an 80 and a 380 kDa fragment of the α2 chain, respectively. The antibodies were visualised by standard methods. A muscle biopsy specimen was available for each case, and was processed with the skin biopsy samples (from the girl a few months previously, from the boy at age 14 days). Skin biopsies were done on four controls with normal expression of laminin α2 on their skeletal muscle fibres. Findings We did not detect laminin α2 in skin specimens from either case, although the controls were positive. The muscle biopsy specimens from the girl showed a few fibres, with traces of laminin α2; those from the boy showed no laminin α2. Interpretation Skin biopsy specimens will provide a useful alternative to muscle biopsy samples for the assessment of laminin-2 (merosin) status in congenital muscular dystrophy.