title: Expression of laminin chains in skin in merosin-deficient congenital muscular dystrophy.
abstract: Laminin-2 (merosin) is a heterotrimer composed of alpha 2, beta 1 and gamma 1 chains. Approximately half of the cases with the classical form of congenital muscular dystrophy (CMD) have a deficiency of the laminin alpha 2 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 alpha 2 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 alpha 2 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 alpha 2 in the skin and severe motor disability, but a normal MRI. Sensory nerves in this case showed normal expression of laminin alpha 2, in contrast to its absence in the severe cases. The expression of laminin beta 1 was also reduced in skin from cases of merosin-deficient CMD. In contrast to human fetal muscle, the laminin alpha 2 protein was not detected in fetal skin up to 23 weeks of gestation. The laminin beta 1 and gamma 1 chains, and the mRNA for laminin alpha 2, however, were present. Studies of mRNA of cultured skin cells suggest that fibroblasts are the major source of laminin alpha 2, 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 alpha 2 protein.
authors.affiliation: Department of Paediatrics and Neonatal Medicine, Royal Postgraduate Medical School, London, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Sewry
authors.forename: M
authors.initials: M
authors.lastname: D'Alessandro
authors.forename: L A
authors.initials: LA
authors.lastname: Wilson
authors.forename: L M
authors.initials: LM
authors.lastname: Sorokin
authors.forename: I
authors.initials: I
authors.lastname: Naom
authors.forename: S
authors.initials: S
authors.lastname: Bruno
authors.forename: A
authors.initials: A
authors.lastname: Ferlini
authors.forename: V
authors.initials: V
authors.lastname: Dubowitz
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6; D046508:Culture Techniques; D005260:Female; D005333:Fetus; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007797:Laminin / Q000032:analysis / Q000172:deficiency*; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D012313:RNA / Q000737:chemistry; D012720:Severity of Illness Index; D012867:Skin / Q000737:chemistry* / Q000473:pathology
chemical_list: D015415:Biomarkers; D007797:Laminin; D012313:RNA