title: Atypical phenotype in two patients with LAMA2 mutations.
abstract: Congenital muscular dystrophy type 1A is caused by mutations in the LAMA2 gene, which encodes the α2-chain of laminin. We report two patients with partial laminin-α2 deficiency and atypical phenotypes, one with almost exclusive central nervous system involvement (cognitive impairment and refractory epilepsy) and the second with marked cardiac dysfunction, rigid spine syndrome and limb-girdle weakness. Patients underwent clinical, histopathological, imaging and genetic studies. Both cases have two heterozygous LAMA2 variants sharing a potentially pathogenic missense mutation c.2461A>C (p.Thr821Pro) located in exon 18. Brain MRI was instrumental for the diagnosis, since muscular examination and motor achievements were normal in the first patient and there was a severe cardiac involvement in the second. The clinical phenotype of the patients is markedly different which could in part be explained by the different combination of mutations types (two missense versus a missense and a truncating mutation).
authors.affiliation: Serviço de Neurologia, Instituto Português de Oncologia de Lisboa, Francisco Gentil, Rua Professor Lima Basto, 1099-023 Lisboa, Portugal. Electronic address: joanarlmmarques@gmail.com.
authors.forename: Joana
authors.initials: J
authors.lastname: Marques
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal; Serviço de Neurologia Pediátrica, Hospital D. Estefânia, Centro Hospitalar Lisboa Central, Rua Jacinta Marto, 1169-045 Lisboa, Portugal.
authors.forename: Sofia T
authors.initials: ST
authors.lastname: Duarte
authors.affiliation: Serviço de Neurologia, Hospital Vila Franca de Xira, Estrada Nacional No. 1, Povos, 2600-009 Vila Franca de Xira, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Costa
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal; Serviço de Neurologia Pediátrica, Hospital D. Estefânia, Centro Hospitalar Lisboa Central, Rua Jacinta Marto, 1169-045 Lisboa, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jacinto
authors.affiliation: Unidade de Genética Molecular, Centro de Genética Médica Dr. Jacinto Magalhães, Centro Hospitalar do Porto, Praça Pedro Nunes, No. 88, 4099-028 Porto, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: Unidade de Genética Molecular, Centro de Genética Médica Dr. Jacinto Magalhães, Centro Hospitalar do Porto, Praça Pedro Nunes, No. 88, 4099-028 Porto, Portugal.
authors.forename: Márcia E
authors.initials: ME
authors.lastname: Oliveira
authors.affiliation: Unidade de Genética Molecular, Centro de Genética Médica Dr. Jacinto Magalhães, Centro Hospitalar do Porto, Praça Pedro Nunes, No. 88, 4099-028 Porto, Portugal; Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal.
authors.forename: Rosário
authors.initials: R
authors.lastname: Santos
authors.affiliation: Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal.
authors.forename: Elsa
authors.initials: E
authors.lastname: Bronze-da-Rocha
authors.affiliation: Laboratório de Neuropatologia, Serviço de Neurologia, Hospital de Santa Maria, CHLN, Av. Professor Egas Moniz, 1649-035 Lisboa, Portugal.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Silvestre
authors.affiliation: Serviço de Neurologia Pediátrica, Hospital D. Estefânia, Centro Hospitalar Lisboa Central, Rua Jacinta Marto, 1169-045 Lisboa, Portugal.
authors.forename: Eulália
authors.initials: E
authors.lastname: Calado
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal; Laboratório de Neuropatologia, Serviço de Neurologia, Hospital de Santa Maria, CHLN, Av. Professor Egas Moniz, 1649-035 Lisboa, Portugal.
authors.forename: Teresinha
authors.initials: T
authors.lastname: Evangelista
mesh_terms: D001921:Brain / Q000473:pathology / Q000503:physiopathology; D009202:Cardiomyopathies / Q000235:genetics / Q000473:pathology; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007797:Laminin / Q000172:deficiency* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D059609:Mallory Bodies / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009136:Muscular Dystrophies / Q000235:genetics / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics / Q000473:pathology; D020125:Mutation, Missense; D010641:Phenotype; D012600:Scoliosis / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: D007797:Laminin; C102645:laminin alpha 2
keywords: Cardiomyopathy; Congenital muscular dystrophy 1A; Epilepsy; Laminin α2-chain; Merosin