Expression of Laminin Chains in Skin in Merosin-Deficient Congenital Muscular Dystrophy

Abstract

Laminin-2 (merosin) is a heterotrimer composed of α2, β1 and γ1 chains. Approximately half of the cases with the classical form of congenital muscular dystrophy (CMD) have a deficiency of the laminin α2 chain, encoded by the LAMA2 gene on chromosome 6q22. This disorder is often termed merosin-deficient CMD. Skeletal and cardiac muscle, and the peripheral and central nervous systems, all express laminin α2 and can be affected in merosin-deficient CMD. Normal skin also expresses all three chains of laminin-2 at the epidermal/dermal junction, around hair follicles and in the sensory nerves. Skin biopsies can therefore be used to assess merosin status in patients. We show here an absence of laminin α2 in skin from four cases of CMD with a severe phenotype and abnormal magnetic resonance image (MRI) of the brain, in contrast to normal expression in one case of mild CMD with normal MRI, and in five controls. An additional case of CMD had a partial deficiency of laminin α2 in the skin and severe motor disability, but a normal MRI.

Sensory nerves in this case showed normal expression of laminin α2, in contrast to its absence in the severe cases. The expression of laminin β1 was also reduced in skin from cases of merosin-deficient CMD. In contrast to human fetal muscle, the laminin α2 protein was not detected in fetal skin up to 23 weeks of gestation. The laminin β1 and γ1 chains, and the mRNA for laminin α2, however, were present. Studies of mRNA of cultured skin cells suggest that fibroblasts are the major source of laminin α2, not keratinocytes. Our data show that skin is useful for the assessment of merosin status in patients with CMD and that skin fibroblasts may be a useful source of tissue-specific RNA. In addition, we show that there is a tissue-specific difference in the developmental expression of the laminin α2 protein.

Key words

Merosin - Laminin - Congenital muscular dystrophy - Skin