title: Genetics of laminin alpha 2 chain (or merosin) deficient congenital muscular dystrophy: from identification of mutations to prenatal diagnosis.
abstract: Congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of muscle disorders, with autosomal recessive inheritance. Absence of the laminin alpha 2 chain in the skeletal muscle of patients with classical CMD has permitted the identification of a subgroup, referred to as 'merosin-deficient CMD or laminin alpha 2 chain deficient CMD'. We first identified a nonsense and a splice site mutation in laminin alpha 2 gene (LAMA2) (Glu1241 stop, 4573-2A-->T). We report here new mutations: nonsense mutations (Glu210stop, Trp2316stop) and 1- and 2-bp deletions (2418 delta C, 6968 delta TA), which result in truncation of the protein either in the short arm domains or in the C terminal globular domain and complete merosin deficiency. Another subgroup, referred to as 'partially-deficient in laminin alpha 2 chain' has been identified recently, and a LAMA2 missense mutation (Cys996Arg) has been shown to cause this partial deficiency. The laminin alpha 2 chain, together with the beta 1 or beta 2 and gamma 1 chains forms either laminin-2 (alpha 2-beta 1-gamma 1) or laminin-4 (alpha 2-beta 2-gamma 1). The LAMA2 mutations induce the formation of abnormal laminins which probably dramatically disturb the assembly and stability of the laminin network, one of the major components of the extracellular matrix in skeletal muscle. We report also the first prenatal diagnosis performed by direct mutation analysis.
authors.affiliation: INSERM U153, Groupe Hospitalier Pitié-Salpétrière, Institut de Myologie, Paris, France. pguichen@myologie.infobiogen.fr
authors.forename: P
authors.initials: P
authors.lastname: Guicheney
authors.forename: N
authors.initials: N
authors.lastname: Vignier
authors.forename: A
authors.initials: A
authors.lastname: Helbling-Leclerc
authors.forename: M
authors.initials: M
authors.lastname: Nissinen
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Cruaud
authors.forename: J C
authors.initials: JC
authors.lastname: Lambert
authors.forename: C
authors.initials: C
authors.lastname: Richelme
authors.forename: H
authors.initials: H
authors.lastname: Topaloglu
authors.forename: L
authors.initials: L
authors.lastname: Merlini
authors.forename: A
authors.initials: A
authors.lastname: Barois
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
authors.forename: F M
authors.initials: FM
authors.lastname: Tomé
authors.forename: K
authors.initials: K
authors.lastname: Tryggvason
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
mesh_terms: D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D007797:Laminin / Q000172:deficiency / Q000235:genetics*; D008297:Male; D009136:Muscular Dystrophies / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D011296:Prenatal Diagnosis
chemical_list: D007797:Laminin